Programmed Death-ligand 1 Immunohistochemical Expression Research Articles

Expression of Programmed Death Ligand 1 and Indoleamine 2,3-Dioxygenase in Oral Lichen Planus and Oral Lichenoid Lesions.

Oral lichen planus (OLP) and oral lichenoid lesions (OLL) are inflammatory T-cell mediated disorders of the oral mucosa (OM). Both are associated with an increased risk of oral squamous cell carcinoma, with OLL possibly having a higher rate of malignant transformation than OLP. Programmed death ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase (IDO) are immunosuppressive molecules possessing inhibitory effect on T-cells and have been implicated in carcinogenesis. The aim of this study was to examine the expression of PD-L1 and IDO in OLP and OLL. Sixty-eight formalin-fixed, paraffin-embedded tissue samples diagnosed as OLP, compatible with OLP, or OLL were divided into OLP (n = 39) or OLL (n = 29) groups based on both clinical and histopathological diagnostic criteria. Samples of healthy OM (n = 9) served as controls. Samples were immunohistochemically stained for PD-L1 and IDO, and staining distribution and intensity were evaluated. Immunohistochemical expression of PD-L1 was increased in the basal and intermediate layers of epithelium in OLP and in lamina propria in both OLP and OLL compared to controls. OLP and OLL showed increased expression of IDO in epithelium and lamina propria compared to controls. PD-L1 staining intensity in the basal epithelial layer, and IDO staining intensity in lamina propria were increased in OLP compared to OLL. The results indicate that the expression of PD-L1 and IDO increases in OLP and OLL, suggesting that these molecules may play a role in the pathogenesis of both disorders.

The prognostic value of programmed death-ligand 1 (PD-L1) expression in resected colorectal cancer without neoadjuvant therapy - differences between antibody clones and cell types

BackgroundProgrammed death-ligand 1 (PD-L1) expression on tumor cells is associated with poor prognosis in several malignancies, while partly contradictory and inconclusive results have been presented for colorectal cancer (CRC). This study aimed to evaluate PD-L1 as a prognostic biomarker in CRC by comparing three different antibody clones.MethodsPatients surgically treated for CRC between January 1st, 2007, and December 31st, 2015, in Kalmar County, Sweden, were retrospectively included. Tissue microarrays from 862 primary tumors without neoadjuvant treatment were assessed for immunohistochemical expression of PD-L1 in tumor cells (TC) and immune cells (IC) using clones 73-10, SP263, and 22C3. Cox regression proportional hazard models were used to estimate hazard ratios for overall survival (OS) and disease-free interval (DFI) in univariable and multivariable analyses, with 1% and 5% set as cut-offs for positive expression in TC and IC respectively.ResultsPD-L1 expression in TC was found in 89 (10%) cases for clone 73-10, 76 (9%) for clone SP263, and 38 (4%) for clone 22C3, while the numbers for IC were 317 (37%) cases for clone 73-10, 264 (31%) for clone SP263, and 89 (10%) for clone 22C3. PD-L1 expression in IC was associated with prolonged OS and DFI in univariable analysis for all three clones. The link to prolonged DFI remained in multivariable analysis for 73-10 and SP263, but only for 73-10 regarding OS. PD-L1 expression in TC was not prognostic of OS in any analysis, while it was associated with prolonged DFI for SP263, and a trend was seen for 73-10. The link to prolonged DFI remained for SP263 and was strengthened for 73-10 in multivariable analysis.ConclusionsThe prognostic value of PD-L1 expression in both IC and TC differs between antibody clones, with 73-10 and SP263 being more reliable for prognostic information than 22C3 in resected CRC.

PD-L1 Immunohistochemical Expression in Endometrial Carcinoma: Egyptian Cross-Sectional Study.

Endometrial carcinoma (EC) is the most common cancer of the female genital tract. According to the recently evolved strategies of cancer immunotherapy, immune checkpoints inhibitors are one of the most crucial strategies. Programmed Death Ligand 1 (PD-L1) is an important immune checkpoint regulator. PD-L1 antibodies have shown efficacy in clinical trials of some malignancies. Some of these antibodies have been approved for clinical usage by the Food and Drug Administration (FDA). This retrospective study included a total of 100 ECs, collected from archived, formalin-fixed, paraffin-embedded tissue blocks of hysterectomy specimens of Egyptian females. The samples were immunohistochemically analyzed for PD-L1 expression (in both tumor cells; TCs and tumor infiltrating leucocytes; TILs) by a semiquantitative score (0 to 4), with cutoff points of (0: <1% of the cells, 1: 1% to 4%, 2: 5% to 9%, 3: 10% to 49%, and 4: ≥ 50%). Membranous staining only was considered positive. PD-L1 was highly expressed in ECs (67% TCs+ and 61% TILs+), with statistically significant relationships with age, lympho-vascular space invasion (LVSI) and TILs score (P = 0.006, 0.016 and <0.005 respectively). However, no statistically significant relationships were detected between PD-L1 expression and the following parameters: histological type, histological grade, pathological stage (pT) or FIGO stage, myometrial, cervical, adnexal/serosal, parametrial involvements and nodal metastasis, as well as ESMO risk stratification system. Moreover, statistically significant relationships were achieved when correlating TILs score with tumor grade and LVSI (P = 0.034 and 0.012 respectively). Also, comparing endometrial hyperplasia (EH) PD-L1 and TCs PDL1 median scores achieved statistically significant relationship (P = 0.001). Our results concluded that PD-L1 expression was greater in both TCs and TILs in a subgroup of patients that have advanced age, LVSI and are TILs-rich, identifying them as potential candidates for anti-PD-1/PD-L1 immunotherapy.

PD-L1 immunohistochemical expression in bladder urothelial cancer with SP263, SP142 and 22C3 antibodies: A comparative study

Programmed death ligand 1 (PD-L1) is currently the only biomarker used for the selection of patients with bladder urothelial cancer for immunotherapy. Several platforms, antibodies and scores are currently available for the evaluation of the expression of PD-L1 in immunohistochemistry (IHC). In this study three different antibodies (SP263, SP142 and 22C3) were compared to establish their performances and concordance rates. Twenty-four consecutive cases of surgically resected urothelial cancers of the bladder were enrolled. All cases were revised, and appropriate tumor areas were selected for IHC. Three commercially available PD-L1 antibodies were tested: 22C3 pharmDx with Dako Autostainer Link 48 (Dako, Carpinteria, Ca), and SP263 and SP142 with the Ventana BenchMark (Ventana Medical Systems, Tucson, AZ) platform. All slides were evaluated by an expert pathologist and both the tumor proportion score (TPS) and the combined positive score (CPS) were determined and compared at two different cut-off levels (≥ 1 and ≥ 10). The SP263 and 22C3 clones produced more positive results with the CPS and TPS scores, respectively. The CPS score identified more positive cases than the TPS score, irrespectively of the clone or the cut-off used; the difference was statistically significant in both the SP263 and SP142 clones with the ≥1 cut-off. No statistically significant differences were found between the clones when the ≥1 cut-off was used, irrespectively of the score. At the contrary, a statistically significant difference (p = 0.024) and a trend to significance (p = 0.082) were respectively found for the TPS and CPS scores, when the SP22C3 and the SP142 clones were compared at a cut-off level of ≥10. The ICC test using CPS was 0.676 and 0.578 for the ≥1 and ≥ 10 cut-offs respectively, and 0.729 and 0.467 respectively for the same cut-offs using TPS. This suggests that the three antibodies under investigation cannot be used interchangeably, especially the 22C3 and SP142 clones which showed statistically significant difference when TPS was tested at a ≥ 10 cut-off.

Immunohistochemical Expression of Programmed Death Ligand- 1 (PD-L1) in Colorectal Carcinoma; A Cross-sectional Study.

Colorectal carcinoma (CRC) is one of the most common cancers worldwide. The interaction of programmed cell death receptor 1 (PD-1) and programmed death ligand 1 (PD-L1) plays an important role by inhibiting the immune mechanism by which cancer cells escape antitumor immunity. Immunotherapy using checkpoint inhibitors is a growing treatment modality in many cancers; one such is anti-PD1/PD-L1. The present study aimed to study the immunohistochemical (IHC) expression of PD-L1 in CRC and its association with various known clinicopathological parameters. This study was a 2-year prospective study and included 34 colectomy specimens diagnosed as colorectal adenocarcinoma. The expression of PD-L1 was evaluated on tumoral cells and tumor-infiltrating immune cells (TIICs) and was correlated with various clinicopathological parameters. Immunohistochemical expression of PD-L1 on tumoral cells and tumor microenvironment in CRC revealed positivity in 17.65% of cases each. The PD-L1 expression on tumoral cells was associated with lymphovascular invasion (LVI) and perineural invasion (PNI) with P- values of 0.012 and 0.005, respectively, while PD-L1 expression on TIICs was associated with tumor budding with a P-value of 0.022. IHC expression of PD-L1 on tumoral cells and immune cells may be associated with some known poor prognostic factors. Since anti-PD1/PD-L1 is used for targeted therapy, it may be beneficial and economically feasible to evaluate PD-L1 in CRC and establish its role as a prognostic factor.

Immunohistochemical Expression of PD-L1 in Core Biopsy Samples of Non Small Cell Lung Cancer and its Association with Histopathological and Clinicoradiological Parameters

Introduction: Lung cancer is one of the most common causes of cancer-related mortality worldwide. In addition to chemotherapy, immunotherapy has yielded favourable outcomes in advanced, surgically non resectable Non Small Cell Lung Carcinoma (NSCLC). The inhibition of immune checkpoints by monoclonal antibodies targeting Programmed Death 1 (PD-1) and Programmed Death Ligand 1 (PD-L1) plays a pivotal role in preventing the downregulation of antitumour immunity. Aim: To study the expression of PD-L1 in NSCLC cases from core biopsy specimens and its association with histological types, grades of tumour along with clinicoradiological parameters (age, sex, smoking status, and radiological location of the tumour). Materials and Methods: This ambispective study was done in the Pathology Department of Kalinga Institute of Medical Sciences, Bhubaneshwar, Odisha, India, over two years from October 2020 to August 2022. The authors studied 35 cases of histopathologically and Immunohistochemically (IHC) diagnosed NSCLC. Partial or complete membranous staining of any intensity in ≥1% of tumour cells was considered positive in IHC. The Tumour Proportion Scoring (TPS) used for PD-L1 reporting was as follows: TPS &lt;1%: negative, TPS 1-49%: low positive expression, and TPS ≥50%: high positive expression. Microsoft excel and Statistical Package for Social Sciences (SPSS) version 25.0 software were used for statistical analysis. Results: The most common age group was 61-70 years (12 cases; 34.29%), with a male predominance 24 (68.60). Chronic smokers (16 cases; 45.71%) were commonly affected. Squamous Cell Carcinoma (SCC) was the common histological type (21 cases; 60%). Overall, 14 cases (40.0%) showed low (1-49%) and 5 cases (14.30%) showed high (≥50%) positive TPS of PD-L1 expression, respectively. Three cases (27.3%) of Grade 2 SCC and one case (10%) of Grade 3 SCC expressed high positivity. There was a statistical association between PDL1 expression and male sex (p-value 0.01), positive smoking history (p-value 0.048), and SCC (p-value 0.032). Conclusion: The PD-L1 expression is associated with increased tumour proliferation, aggressiveness, as well as shorter survival period in advanced NSCLC. The present study showed a significant association of PD-L1 expression in males, chronic smokers, and SCC. As per the existing literature, its association with clinicoradiological parameters is not clear. Future research with a larger cohort study, along with other predictive biomarkers, is highly desired to reach conclusive evidence.

Evaluation of immune density, PD-L1, and CXCR4 expressions in metaplastic breast carcinoma to predict potential immunotherapy benefit.

Metaplastic breast carcinoma (MBC) -rare but fatal subtype of invasive breast carcinomas- provides limited benefit from conventional triple-negative breast carcinoma chemotherapy. We aimed to determine the immune density of this tumor and to evaluate of programmed death-ligand 1 (PD-L1) and chemokine receptor type 4 (CXCR4) expressions to determine whether it would benefit from immunotherapy. Clinicopathological characteristics of 85 patients diagnosed as MBC between 1997 and 2017 were retrospectively assessed. We evaluated the immunohistochemical expression of PD-L1 and CXCR4, and the extent of tumour infiltrating lymphocytes (TILs), with survival data. TILs groups were statistically significantly associated with lymph node status, histological subtype, squamous component, local recurrence and/or systemic metastasis, and disease-related deaths (p < 0.05). PD-L1 positivity in immune cells (ICs) has a statistically significant relationship with the presence of squamous component (p = 0.011) and HER2 positivity (p = 0.031). PD-L1 positivity in tumor cells (TCs) was found to be significantly more frequent in high-TILs density (p = 0.003). PD-L1 combined positive score was significantly associated with the tumors containing high-TILs density (p = 0.012) and squamous component (p = 0.035). Disease-free and disease-specific survival rates were found to be longer for the cases displaying PD-L1 positivity in ICs; and also PD-L1 positivity in ICs was found to be an independent prognostic factor. When the expression of CXCR4 was compared with clinicopathological and survival parameters, no statistically significant association was found (p > 0.05). Based on the results of this retrospective study, PD-L1 and TILs appear to be prognostic. This study provides rationale for further studies to determine whether a subset of patients with metaplastic breast cancer could derive a meaningful benefit from immune-targeting therapies.

Evaluation of Programmed Death - Ligand 1 (Pd-L1) Expression in Head and Neck Squamous Cell Carcinoma.

Head and Neck Squamous Cell Carcinoma (HNSCC) is a highly frequent malignancy worldwide and is also the leading cause of death. The prognosis for individuals with HNSCC remains dismal, with a five-year survival rate of less than 50%. The novel anti-PD-L1 immunotherapy is found to be promising, and immunohistochemistry (IHC) has been established as a reliable method for patient stratification. We intend to evaluate the prognostic significance of the expression of programmed death ligand-1 (PD-L1) in HNSCC and determine its association with clinicopathological variables. A total of 50 cases of biopsy-confirmed HNSCC were studied in a tertiary hospital between Dec 2020 and June 2022. The specimens were tested for PD-L1 IHC expression with antibody clone CAL-10 (Biocare) and scored by Combined Positive Score (CPS). The association between PD-L1 expression and clinicopathological variables was evaluated. PD-L1 was positive in 92% of the cases, and a significant association (P= 0.024) was seen between PD-L1 expression and tumor-infiltrating lymphocytes (TILs). PD-L1 did not show any significant association with patient demographics, tumor site, grade, or stage. In the present study, evaluation of the immunohistochemical expression of PD-L1 on the tumor cells and TILs in HNSCC revealed a high prevalence of PD-L1 expression. PD-L1 IHC studies for patient selection for immunotherapy would be a promising technique. Frequent PD-L1 expression in tumors with significant TILs may be useful in identifying patients who may benefit from anti-PD-1/PD-L1 therapy.

Effect of Radio-Chemotherapy on PD-L1 Immunohistochemical Expression in Head and Neck Squamous Cell Carcinoma

Programmed death-ligand 1 (PD-L1) checkpoint inhibitors represent a mainstay of therapy in head and neck squamous cell cancer (HNSCC). However, little is known about the influence of combined therapy on PD-L1 expression. The study aims to gather evidence on this topic. A systematic search was carried out in electronic databases Pubmed-MEDLINE and Embase to retrieve studies on the comparison of PD-L1 expression before and after conventional therapy. Data were extracted and a quantitative analysis with pooled odds ratios (ORs) was performed when applicable. Of 5688 items, 15 were finally included. Only a minority of studies assessed PD-L1 with the recommended combined positive score (CPS). The results are highly heterogeneous, with some studies reporting an increase in PD-L1 expression and others reporting a decrease. Three studies allowed for quantitative analysis and showed a pooled OR of 0.49 (CI 0.27-0.90). From the present evidence, a clear conclusion towards an increase or decrease in PD-L1 expression after combined therapy cannot be drawn, but even with few studies available, a trend towards an increase in expression in tumor cells at a cutoff of 1% can be noted in patients undergoing platinum-based therapy. Future studies will provide more robust data on the effect of combined therapy on PD-L1 expression.

Immunohistochemical Expression of PD-L1 and IDH1 with Detection of MGMT Promoter Methylation in Astrocytoma

Programmed death ligand 1 (PD-L1) expression was suggested as a poor prognostic predictor for glioblastoma. While isocitrate dehydrogenase (IDH) has been linked to enhanced overall survival in glioma cells. In glioblastoma patients receiving treatment with alkylating drugs, the methylguanine-DNA methyltransferase (MGMT) promoter's methylation status has been discovered as a potent and distinct predictor of good survival. In this study, we aimed to investigate the expression rate of PD-L1, IDH1, and MGMT methylation in patients with different grades of astrocytoma. The present retrospective study retrieved the data and archived paraffin blocks of 60 cases of astrocytoma. Immunohistochemical evaluation was done to assess the expressions of PD-L1 and IDH1, Methylation-specific-PCR was used to investigate the MGMT promoter. This study included astrocytoma grade II 18% (11/60), grade III 22% (13/60), grade IV 60% (36 cases). PD-L1 expression was detected in 82% of all studied cases (49/60) while IDH1 mutant astrocytoma were 73% (44/60) & methylation was reported in 58.3% (35 cases). High grade astrocytoma showed highrer expression of PD-L1 & IDH1 but with insignificant correlation (p=0.989). There is a relatively high expression of PD-L1 and IDH1 in patients with astrocytoma. More than half of the patients presented with MGMT promoter methylation. Further studies with larger sample size are required to investigate the association between these biomarkers and characteristics of patients with astrocytoma.

Programmed death-ligand 1 (PD-L1) expression in Hodgkin’s lymphoma among Peruvian patients

Objective: Various studies on Hodgkin’s lymphoma (HL) have determined programmed death-ligand 1 (PD-L1) expression in Hodgkin and Reed-Sternberg (HRS) cells, with variable results. This protein has gained relevance for its role in theimmune response in malignant neoplasms. This work aimed to determine PD-L1 immunohistochemical expression in HRS cells and its relationship with age, sex, clinical stage and overall survival (OS) in a cohort of Peruvian patients. Materials and methods: Twenty-five (25) biopsies from patients diagnosed with HL were assessed, which allowed determining PD-L1 immunohistochemical expression in HRS cells in relation to OS and clinical data of the patients. Results: All cases showed PD-L1 expression in more than 1 % of tumor cells. There was no statistically significant difference in OS when two groups were compared in terms of PD-L1 expression with a cut-off point of 50 %, clinical stage (CS), age and sex. Conclusions: High PD-L1 expression was found in pre-treatment HL tumors. No association was found between PD-L1 expression, OS, age, sex or CS. Further studies with a larger number of patients are necessary to reassess the prognosticimpact of the expression of this protein in HL.

PD-L1-Positive High-Grade Triple-Negative Breast Cancer Patients Respond Better to Standard Neoadjuvant Treatment-A Retrospective Study of PD-L1 Expression in Relation to Different Clinicopathological Parameters.

Triple negative breast cancer (TNBC) is typically a high-grade breast cancer with poorest clinical outcome despite available treatment modalities with chemo-, immuno- and radiotherapy. The status of tumor-infiltrating lymphocytes (TILs) is a prognostic factor closely related to programmed death ligand 1 (PD-L1) expressed on T lymphocytes modulating antitumor immunity. Immune-checkpoint inhibitors (ICI) are showing promising results in a subset of breast cancer patients in both neo- and adjuvant settings. Pathologic complete response (pCR) after neoadjuvant treatment was found to be associated with better prognosis. We analyzed the prognostic and predictive significance of PD-L1 (SP142 assay) immunohistochemical expression on TNBC patients’ samples as illustrated by pCR with regard to its relation to treatment regimen, stage, BRCA mutational status and outcome. Furthermore, we analyzed a few other clinicopathological parameters such as age, TILs and proliferation index. The study highlighted a positive role of PD-L1 evaluation for personalized pCR probability assessment. Although considerable research was made on comparison of PD-L1 level in TNBC with different patient parameters, to our best knowledge, the relation of PD-L1 status to pCR while taking treatment regimen and stage into consideration was so far not investigated.

Evaluation of Programmed Death Ligand-1 Immunohistochemical Expression and Tumor-Infiltrating Lymphocytes in Different Types of Endometrial Carcinoma

BACKGROUND: Endometrial cancer (EC) identified at an early stage is successfully treated in a majority of patients with surgery with or without radiotherapy or chemotherapy. For patients with advanced disease, however, the prognosis is poor; 5-year survival rates are less than 50% in patients with lymph node metastases and less than 20% with peritoneal or distant metastases. Previous studies proved that programmed death-1/programmed death ligand-1 (PD1-/PD-L1) blockers are currently effectively used as immunotherapies in a number of tumors such as melanoma and non-small cell lung cancer. AIM: This study was conducted to determine the expression of PD L1 in endometrial carcinoma and to assess its potential role as a biomarker for different types that can be used to screen candidates fit for immunotherapy. MATERIALS AND METHODS: This cross-sectional study was carried out on 32 cases of endometrial carcinoma cases that underwent endometrial biopsies, dilatation, and curettage or radical hysterectomies at Ain Shams University Hospitals Pathology Units from 2018 to 2020 with their clinical and radiological assessments. Correlation between hematoxylin and eosin-stained histopathological sections and PD-L1 immunohistochemical staining of the same sections, mainly emphasizing the tumor-infiltrating lymphocytes, was done. RESULTS: PDL-1-positive expression of both tumor cells and TILs was significantly more frequent in type II endometrial carcinoma (p = 0.04 and 0.03, respectively) using a cut-off value 10%, compared to type I. Moreover, Grade III tumors showed significantly more frequent PDL-1 expression in both tumor cells and TILs than Grade I and II tumors, using 5% and 10% cut-off values indicating that PDL-1 is overexpressed in aggressive tumors. CONCLUSION: PD-L1 staining is significantly related to high-grade tumors and type II endometrial carcinomas, the aggressive types, which support their probable benefit from immunotherapy. Separate assessment of PD-L1-positive staining in both tumor cells or TILs with a cut-off value 10% can significantly reflect the aggressiveness of the tumor and its probable benefit from immunotherapy.

Abstract P5-13-17: PD-L1 expression in breast to brain metastases

Abstract Background Brain metastases (BrM) are a major cause of morbidity and mortality in women with breast cancer. Immunotherapy has the potential for intracranial efficacy among patients with breast cancer since intracranial response to immunotherapy has been observed among patients with other solid tumors. The aim of the study is to analyze the immunohistochemical expression of programmed death ligand 1 (PD-L1), a predictive biomarker of response to immunotherapy, in breast cancer BrMs. Methods A retrospective cohort study of consecutive patients who underwent surgery for breast cancer BrM at Sunnybrook Health Sciences Centre between July 1999 and June 2013 were identified through the Anatomic Pathology departmental database. A tissue microarray using 1um cores was obtained. Immunohistochemical expression of PD-L1 in BrM tissue was assessed in triplicate; PD-L1 positive status was defined as PD-L1 expression ≥1% in tumor infiltrating cells as a percentage of tumor area using the Ventana SP142 antibody. Estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor (HER2) status was determined using 2018 ASCO/CAP guidelines. Results The median patient age at the time of BrM diagnosis was 52 (range 32-85). ER, PR and HER2 status was available in 58 of 59 cases as follows: 12 (20.3%) triple negative (TNBC), 14 (23.7%) HER2+/HR-, 14 (23.7%) HER2+/HR+, 18 (30.5%) hormone receptor (HR)+/HER2-. The majority 62.7% (n=37) of patients had a solitary BrM. The median size of BrM was 2.9 cm (range 0.3 cm to 6.2 cm) with the most common location being the cerebellum and frontal lobe. The majority of patients (n=51, 86.4%) had symptomatic BrM. The most common sites of extra-cranial metastases were bone (37%), lung (32%), liver (22%), lymph nodes (18.6%), and chest wall (3.4%). After surgical excision of BrM, 88.1% of patients received adjuvant stereotactic radiosurgery (SRS) or whole brain radiotherapy (WBRT). 39% of patients received at least 1 line of systemic therapy for metastatic disease prior to the development of BrM. The median follow-up for BrM events was 16.1 months. PD-L1 status was available for all 59 patients. In the overall cohort, 9 out 59 (15.3%) breast cancer BrM were PD-L1 positive irrespective of subtype. The frequency of PD-L1 positive BrM by subtype is as follows: TNBC (n= 3/12, 25%), HER2+/HR- (n=3/14, 21.4%), HER2+/HR+ (n=1/14, 7.1%), and HR+/HER2- (n=2/18, 11.1%). Expression of PD-L1 in BrMs was not associated with patient age at the time of BrM diagnosis, size or location of the BrM, grade of the BrM nor breast cancer subtype. At 24 months, brain-specific progression-free survival (bsPFS) was 47.5% (95% CI 32.9-68.7%). When stratified by PD-L1 status, 24-month bs-PFS was 66.7% (95% CI 37.9-100%) among patients with PD-L1 positive BrM versus 42% (95% CI 26.6-67.3%) among those with PD-L1 negative BrM (log-rank p-value 0.142). Conclusion One in 7 patients in our cohort had PD-L1 positive BrM; this proportion was highest (25%) among those with TNBC. Hence, there is rationale to include patients with breast cancer BrM in clinical trials evaluating efficacy of immunotherapy. Citation Format: Rania Chehade, Maleeha A Qazi, Marguerite Ennis, Sharon Nofech-Mozes, Katarzyna Jerzak. PD-L1 expression in breast to brain metastases [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-13-17.

The role and relationship between programmed death ligand 1 and cytotoxic T lymphocyte-associated antigen-4 immunohistochemical expression in colorectal carcinoma patients: an impact on outcome.

BackgroundGlobally, colorectal carcinoma (CRC) is the third most common cancer diagnosed in both men and women. Programmed death ligand 1 (PD-L1) and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) are immune checkpoints that induce tumour immune escape.AimThis study aimed to evaluate the immunohistochemical expression of PD-L1 and CTLA-4 in CRC and their relationship with clinicopathological parameters and survival data.ResultThis study included 103 CRC, 22 adenoma and 21 non-neoplastic specimens. High PD-L1 epithelial expression was in favour of CRC and high-grade dysplastic adenoma compared to normal specimens. High PD-L1 epithelial expression was associated with larger sized tumours, perforation, advanced T stage, infiltrative tumour border configuration (TBC), high tumour budding (TB) score, low tumour-stroma ratio (TSR) and absence of peritumoural lymphocytes. High PD-L1+ tumour infiltrating lymphocytes (TILs) showed an association with absence of perforation, early T stage, pushing TBC, lower TB score, high TSR and presence of peritumoural lymphocytes. High epithelial CTLA-4 expression was in favour of adenocarcinoma, high-grade dysplastic adenoma and low-grade dysplastic adenoma compared to normal specimens. High CTLA-4 epithelial score showed an association with positive lymph nodes (LNs), presence of an infiltrative TBC and absence of peritumoural lymphocytes. Low CTLA-4+ TILs showed a significant association with advanced tumour stage and increased number of positive LNs. Prolonged survival was associated with low epithelial PD-L1 and CTLA-4, high PD-L1+ TILs and high CTLA-4+ TILs. By multivariate Cox regression analysis, PD-L1+ TILs immunoreactivity score (p = 0.020) and CTLA-4+ TILs H. score (p = 0.036) were independent prognostic factors affecting overall survival among the other prognostic factors.ConclusionPD-L1 and CTLA-4 expression by tumour cells could cooperate with each other in enhancing progression of CRC leading to poor patient outcome, while their expression by TILs could stand against tumour progression.

PDL-1 expression in lung carcinoma and its correlation with clinicopathological and prognostic characteristics

ABSTRACT Lung cancers have high incidence and high mortality rates. The immune checkpoints as programmed death ligand 1 (PDL-1) can suppress the tumor immune reaction. So, their blocking seems to be a way to treat tumors. This study assesses PDL-1 immunohistochemical expression in lung cancer, and its correlation with prognosis. It included 62 specimens of lung cancer in Hospitals of Mansoura Faculty of Medicine, Egypt. Seventy-one percent of cases showed positive PDL-1 and about 59.1% of them showed high expression. PDL-1 expression in NSCLC was significantly higher than in SCLC (P = 0.019). There were no significant associations between PDL-1 expression and other clinicopathological parameters. A significant mild positive correlation between PDL-1 and EGFR marker was found (P = 0.006). The mean overall survival in cases with positive PDL-1 was lower than negative cases (P = 0.37). Also, progression-free survival was lower among PDL-1 positive cases compared to negative cases (P = 0.5). This study reports that immune checkpoint, PDL-1 is overexpressed in lung cancer especially NSCLC. It is correlated with EGFR overexpression. PDL-1 could have potential to be an effective immune target for lung cancer immunotherapy. But the presence of PD-L1-negative tumors highlights the importance of searching for alternative or combination treatment strategies. Abbreviations: AC: Adenocarcinoma; COPD: Chronic Obstructive Pulmonary Diseases; CTLA-4: Cytotoxic T-lymphocyte-associated protein 4; EGFR: Epidermal Growth Factor Receptor; IHC: Immunohistochemical; NSCLC: Non-Small Cell Lung Cancer; OS: Overall Survival; PD1: Programmed Death 1; PDL-1: Programmed Death ligand 1; PFS: Progression Free Survival; SCC: Squamous cell carcinoma; SCLC: Small Cell Lung Cancer; SD: Standard Deviation; TCR: T-cell receptor; TPS: Tumor Proportion Score.

Expression of programmed death ligand 1 (PD-L1) in urothelial bladder carcinoma (immunohistochemical and histopathological study)

The aim of this work is to evaluate the immunohistochemical expression of PD-L1 in tumor cells of urothelial bladder carcinoma. PD-L1 immunoexpression was assessed on 20 cases of radical cystectomy specimens using monoclonal rabbit anti- PD-L1 antibody. Extent of membranous PD-L1 expression was assigned in each case. Tumor cells showing > 5% expression were considered positive. PD-L1was seen in 6 (30%) cases [1 case score +2 and 5 cases score +3], while 14(70%) cases were negative [7 cases score 0 and 7 cases score +1]. PD-L1 expression in tumor cells was insignificantly correlated with different available clinicopathological parameters such as sex, pathological stage, associatedbilharzial infestation, necrosis, perineural invasion and associated tumor infiltrating mononuclear cells (TIMCs), although PD-L1 positivity tend to predominate in advanced pathological stage of tumor (T3 and T4). These findings may have clinical implications for the management of patients with PD-L1 positive urothelial bladder carcinoma.

Expression of Immune Checkpoint Regulators, Cytotoxic T-Lymphocyte Antigen-4, and Programmed Death-Ligand 1 in Epstein-Barr Virus-associated Nasopharyngeal Carcinoma.

Nasopharyngeal carcinoma (NPC) is the most common cancer arising from the nasopharynx with a poor prognosis. Targeting immune checkpoint is one of the new promising lines in cancer treatment. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed death-ligand 1 (PD-L1) are immune checkpoints that regulate T-cell immune function. This work aimed to assess the immunohistochemical expression of PD-L1 and CTLA-4 in NPC and their ability to predict survival and response therapy and to check their validity as immunotherapy targets. Twenty-six cases of NPC were studied by immunohistochemistry for PD-L1 and CTLA-4 and by nested polymerase chain reaction followed by DNA sequencing for the presence of EBNA-1 gene of Epstein-Barr virus (EBV). All investigated cases were diagnosed and treated in the Zagazig University Hospital in the period from August 2015 to July 2018. EBNA-1 gene was identified in 84.6% of the cases. Whereas the expression of PD-L1 was noted in 46.2% of all cases studied, 54.6% of EBV-associated NPCs were found to express PD-L1. There was a significant association between PD-L1 expression and the advanced stage of the tumor (P<0.001). CTLA-4 expression was observed in 88.4% of all NPC cases as cytoplasmic staining in both tumor cells and tumor-infiltrating lymphocytes. CTLA-4 expression in lymphocytes was associated with the presence of EBV. A significant association was detected between CTLA-4 and tumor-infiltrating lymphocyte expression on one side and the stage of the tumor on the other. High expression of CTLA-4 was significantly associated with disease progression and worse overall survival. PD-L1 and CTLA-4 are adverse prognostic markers in NPC. The authors propose that targeted therapy against PD-L1 and CTLA-4 will be a hopeful therapy for cases of NPC with resistance to concurrent chemoradiation treatment in Egypt, especially EBV-associated cases.

Programmed death ligand 1 protein expression is positively correlated with the solid predominant subtype, high MIB-1 labeling index, and p53 expression and negatively correlated with epidermal growth factor receptor mutations in lung adenocarcinoma

Programmed death ligand 1 (PD-L1) protein expression is a proposed predictive biomarker of immunotherapy; thus, identification of the clinicopathological and molecular characteristics associated with PD-L1 expression is important and necessary. We examined PD-L1 immunohistochemical expression and its relationships with the clinicopathological and molecular characteristics of patients with surgically resected nonsmall cell lung carcinoma. PD-L1 expression differed according to the histological subtype. Among 633 patients with adenocarcinoma, 523 (82.6%) had no PD-L1 expression, 78 (12.3%) low expression, and 32 (5.1%) high expression. PD-L1 expression was more common in men (p<0.001), in smokers (p=0.002), and in patients with a more advanced stage (p=0.002), the solid predominant subtype (p<0.001), no epidermal growth factor receptor(EGFR) mutations (p<0.001), a high MIB-1 labeling index (p<0.001), and positive p53 immunohistochemical expression (p<0.001). In a multivariate logistic regression analysis, the solid predominant subtype (odds ratio [OR]=4.92, 95% confidence interval [CI]: 2.72-8.89, p<0.001), no EGFR mutations (OR=2.27, 95% CI: 1.35-2.7, p=0.002), a high MIB-1 labeling index (OR=2.78, 95% CI: 1.72-4.55, p<0.001), and p53 positivity (OR=2.13, 95% CI: 1.34-4.36, p=0.042) were significantly and independently associated with PD-L1 expression. The combination of the solid predominant subtype with a high MIB-1 labeling index was strongly associated with positive expression of PD-L1. In the 193 patients with squamous cell carcinoma, 92 (47.7%) had no PD-L1 expression, 57 (29.5%) low expression, and 44 (22.8%) high expression. There were no significant correlations between PD-L1 expression and the evaluated clinicopathological or molecular characteristics of these patients. These results, indicating associations of PD-L1 with various clinicopathological or molecular characteristics in adenocarcinoma but not squamous cell carcinoma, may be useful for selecting patients with a good response to immune checkpoint inhibitors.

Metaplastic breast cancers frequently express immune checkpoint markers FOXP3 and PD-L1

BackgroundMetaplastic breast carcinoma encompasses a heterogeneous group of tumours with differentiation into squamous and/or spindle, chondroid, osseous or rhabdoid mesenchymal-looking elements. Emerging immunotherapies targeting Programmed Death Ligand 1 (PD-L1) and immune-suppressing T cells (Tregs) may benefit metaplastic breast cancer patients, which are typically chemo-resistant and do not express hormone therapy targets.MethodsWe evaluated the immunohistochemical expression of PD-L1 and FOXP3, and the extent of tumour infiltrating lymphocytes (TILs) in a large cohort of metaplastic breast cancers, with survival data.ResultsMetaplastic breast cancers were significantly enriched for PD-L1 positive tumour cells, compared to triple-negative ductal breast cancers (P < 0.0001), while there was no significant difference in PD-L1 positive TILs. Metaplastic breast cancers were also significantly enriched for TILs expressing FOXP3, with FOXP3 positive intra-tumoural TILs (iTILs) associated with an adverse prognostic outcome (P = 0.0226). Multivariate analysis identified FOXP3 iTILs expression status as an important independent prognostic factor for patient survival.ConclusionsOur findings indicate the clinical significance and prognostic value of FOXP3, PD-1/PD-L1 checkpoint and TILs in metaplastic breast cancer and confirm that a subset of metaplastics may benefit from immune-based therapies.