Immune Contexture Research Articles

Intra-Tumoral CD8+:CD3+ Lymphocyte Density Ratio in Appendix Cancer Is a Tumor Volume- and Grade-Independent Predictor of Survival

Background: The immune contexture of solid tumors plays a critical role in cancer progression and response to immunotherapy. However, immunologic characterization of appendiceal cancer (AC) has lagged behind advancements in other gastrointestinal malignancies. This study aims to define the AC immune microenvironment by quantifying CD3+ and CD8+ lymphocyte densities and assessing their prognostic significance. Methods: Archival tissue samples from 95 AC patients were analyzed using immunohistochemistry to assess CD3+ and CD8+ T cell densities and their ratios. Associations between lymphocyte density and clinical, pathologic, and oncologic variables were examined using Spearman’s correlation, Kruskal–Wallis tests, and Cox proportional hazards analysis. Results: Tumor samples exhibited substantial immunologic heterogeneity with significant rightward skew. CD3+ and CD8+ densities were higher in low-grade tumors (p = 0.02 and p = 0.01, respectively) and low-grade histologic subtypes (p = 0.01 and p = 0.006). Lymphocyte density was inversely associated with patient age and was significantly lower in high-grade and non-mucinous tumors. The CD8+:CD3+ ratio emerged as an independent prognostic marker for progression-free survival (HR = 0.39, p = 0.004), whereas absolute CD3+ and CD8+ densities were less predictive. Conclusions: This study highlights the diverse immune microenvironment in AC, with immune infiltration patterns correlating with tumor grade and histologic subtype. The CD8+:CD3+ ratio is a potential prognostic biomarker for patient stratification, underscoring its clinical significance. Future studies should expand immune biomarker panels and explore immunomodulatory therapies for lymphocyte-rich AC subsets.

Identification of m6A methyltransferase-related WTAP and ZC3H13 predicts immune infiltrates in glioblastoma

Glioblastoma (GBM) is a prevalent and highly fatal primary malignant brain tumor. N6-methyladenosine (m6A) modification plays a critical role in the development of brain tumor. WTAP and ZC3H13 have been identified across various species. Immune contexture, which includes the tumor microenvironment (TME), plays a significant role in cancer progression and treatment. This study aimed to explore the potential impact between WTAP and ZC3H13 on the immunological characteristics of GBM. We utilized data from TCGA-GBM, GEO and CGGA datasets to obtain platform and probe data. Patients with GBM were stratified into two clusters based on the expression of WTAP and ZC3H13 using consensus clustering approach. Immune infiltration within the tumor microenvironment was assessed using ESTIMATE, CIBERSORT and ssGSEA methodologies. Functional disparities were determined through gene set enrichment analysis (GSEA). Tumor mutation burden (TMB) and immune checkpoint inhibitors (ICIs) were also analyzed. Co-expression network analysis (WGCNA) was used to identify genes associated with WTAP/ZC3H13 and immunity. Validation was performed using GEO and CGGA datasets. Our analysis revealed that cluster1 exhibited higher WTAP expression but lower ZC3H13 expression compared to cluster2. Cluster1 showed higher levels of immune infiltration and TMB compared to cluster2. WGCNA identified 15 genes closely associated with WTAP/ZC3H13 expression and immune scores, notably CTLA4, CD27, ICOS, and LAG3. Our results suggested that WTAP and ZC3H13 influence on immune contexture of GBM, providing new insights into tumor immunity in GBM.

A novel immune-based score and its immune contexture exploration in colorectal cancer.

234 Background: The majority of currently available biomarkers in colorectal cancer (CRC) perform poorly with respect to prognostication and prediction of response. Immunoscore (IS) has been proposed as a signature of host immune cancer response reflecting a favorable prognosis. Next, through AtezoTRIBE, ‘Immunoscore immune checkpoint’ (IS-IC) was introduced, indicating its potential predictive value for immune checkpoint blockade (ICB) in pMMR metastatic CRC. IS-IC is computed through quantitative and spatial variables related to density and proximity of CD8 cells and programmed cell death-ligand 1 (PD-L1) cells in the tumor core (TC). There are little confirmatory studies. In this work we test the application of IS-IC through multiplex immunofluorescence (mIF) on our own cohort of patients. Next we explore immune contexture differences through subgroup analysis. Methods: 15 prospectively collected, treatment naïve, primary CRC samples (9 dMMR/MSI-H, 6 pMMR/MSS) where analyzed with mIF. Cell density, proximity between cells, cell clustering and spatial distribution of selected mIF biomarkers (CD3, CD20, CD11c, CD163, CD15, CD4, CD8, Foxp3, CD56, Granzyme B, PD-L1, programmed cell death protein 1 (PD-1), pan-cytokeratin (CK) and Ki67) were analyzed both at the invasive margin (IM) and TC using digital pathology. All slides subjected to digital image analysis met predefined quality control criteria. Results: Serial mIF showed PD-L1 was enriched in stromal cells (CK - ) within IM ( p =0.0148) and confirmed its co-localization with macrophages (CD163 + ) ( p =0.0092). Hence, both TC and IM were included to quantify the densities of CD8, PD-L1 and the proximity between them, as a suggested novel IS-IC TC+IM . During exploration of the immune context we found that both IS-IC and IS-IC TC+IM high groups exhibited significantly increased infiltration of PD-1 + cells ( p =0.0074 and p =0.0058, respectively) and CD8 + PD-1 + cells ( p =0.0101 and p =0.0062, respectively), compared to the corresponding low groups. Whereas only the IS-IC TC+IM high group showed increased natural killer (NK) cells (CD56 + ) ( p =0.0192), found mainly at IM ( p =0.0167) in contrast to TC ( p =0.0824). The novel IS-IC TC+IM scoring system captures the immunosuppressive and immune responsive interaction among PD-1 + cells, PD-L1 + cells, NK cells and CD8 + cells in TC and IM from the cell numbers and cell-cell proximity. A validation cohort is underway. Conclusions: In this study we confirm the ease of replicating IS-IC and the presence of ICB sensitive stroma in the high score group. This study further explored the immune context in both TC and IM, emphasizing the importance of regional differences. Additionally it was found that NK cells were only increased at IM. Altogether we suggests adding dual quantification in TC and IM as a novel IS-IC TC+IM , which may be a more sufficient reflection of the tumor micro environment.

Immune cells in thyroid adenoma and carcinoma: uncovering a hidden value of assessing tumor-host interplay and its potential application in thyroid cytopathology

IntroductionAlthough the role of tumor immune microenvironment (TIME) in thyroid cancer is well established, little data exists about the differences in immune cell presence in thyroid adenomas and carcinomas. We assume that immune cell density could be an additional diagnostic criterion for differentiating benign and malignant tumors in thyroid aspirates.AimThe current study compared the immune contexture of thyroid adenoma (TA) and thyroid carcinoma (TC) in histological and cytological specimens of III-V categories.Materials and methodsThis pilot study included 72 cases (36 of TA and 36 of TC) with verified histological diagnosis and pre-operative cytology corresponding to categories III, IV and V according to the Bethesda system for reporting thyroid cytology. The number of CD8+, CD68+ and CD163+ cells was assessed in histological samples of TA and TC with further comparison to cytological specimens. Besides, the expression of STAT6 and SMAD4 as potential regulators of TIME was evaluated in the study.ResultsTC demonstrated an immune-rich profile representing abundant tumor-associated CD8+ lymphocytes, CD68 and CD163+ macrophages. In contrast, TA represented mostly a low immune cell infiltration. The higher immunogenicity of TC was accompanied by the more profound expression of STAT6 and SMAD4 in tumor cells. The number of immune cells in cytological specimens correlated with CD8+ (r = 0.693; p < 0.001) and CD163+ cells (r = 0.559; p < 0.001) in histological samples, reflecting the differences in the tumor immune microenvironment between benign and malignant thyroid neoplasms.ConclusionTC demonstrated high immunogenicity compared to TA, which correlated to the number of immune cells in cytological specimens. The number of immune cells in thyroid cytology samples could be an additional criterion in cytological diagnostics for III-V Bethesda categories. Further investigations are needed to validate the findings of the study.

Abstract P021: Countering adenosine (ADO) in rectal cancer to improve RT responses to immune checkpoint blockade: a trial to test the safety and efficacy of PD1 (AB122) and ADO dual receptor (AB928) antagonists with chemotherapy after short-course RT

Abstract Background: Rectal cancer (RC) is unresponsive to single agent immune checkpoint blockade (ICB), with the exception of microsatellite instability (MSI) high tumors. Neoadjuvant radiotherapy (RT), however, is a standard treatment for locally advanced RC. A recent analysis of RC showed that upregulation of genes reflecting an increased T cell-inflamed and IFN-I response in post-RT samples compared with pre-RT biopsies correlated with pathological responses. The efficacy of combining RT with ICB in RC remains a focus of several ongoing and recently reported clinical trials. Extracellular adenosine (eADO) signaling, an important immunosuppressive pathway in RC, may hinder immune activation as TCGA and our preclinical data, respectively, suggests that eADO generation and signaling is elevated at baseline and exacerbated by RT. In mouse models, the inhibition of eADO generation improved systemic responses to ICB in otherwise refractory tumors. HypothesisWe hypothesize that inhibition of ADO signaling in RC is safe and an effective method to enhance RT-induced anti-tumor T cell responses as a means to sensitize RC to RT and anti-PD1 therapy. Brief Methods: NCT05024097, PANTHER RC trial, is a prospective phase I-II neoadjuvant study in patients with locally advanced RC. Patients receive upfront (wk 1) SC-RT (25 Gy in 5 fx) to the pelvis in combination with the dual A2aR/A2bR (adenosine receptors) inhibitor etrumadenant (AB928). Chemotherapy (wks 3-15), mFOLFOX x 6 cycles, is given with etrumadenant and anti-PD1 antibody zimberelimab (AB122). All patients undergo clinical response assessment (weeks 17-20) followed by watch and wait (if cCR) or total mesorectal excision for pathologic response assessment. The primary endpoint is the proportion of patients who achieve a CR. Secondary endpoints include 3-year disease-related treatment failure and 5-year overall survival. Part I is a modified 3+3 safety run-in for etrumadenant plus SC-RT. Part II is an open label single arm Simon’s 2-stage optimal design. With a sample size of 27 patients (stage 1 = 15 patients and stage 2 = 12 patients) the trial is powered to detect a CR rate of 25% or less versus the atlernative, at least 45%. Results: To date 21 patients have enrolled. One of six patients accrued to part I experienced a grade 3+ treatment related toxicity. A CR was observed in one of five (20%) evaluable patients. In part II, the first eleven of fifteen accrued patients to stage 1 completed treatment and were assessed for response. A CR rate of 82% (4 pCRs, 5 cCRs, 2 pPRs) was observed. The trial is anticipated to proceed to stage 2 and accrue an additional twelve patients (27 total). Conclusion: The preliminary responses are promising and patient enrollment is ongoing. Tumor biopsies, blood specimens, and stool samples before and after RT will be comprehensively analyzed to determine the immune contexture at baseline, during, and after therapy. Correlative studies will help determine whether RT with ADO signaling blockade produces anti-tumor T cells capable of achieving CRs in locally advanced RC. Citation Format: Encouse Golden, Sandra Demaria, Nir Ben Chetrit, Mehraneh Dorna Jafari, Manish Shah, Silvia Formenti.Countering adenosine (ADO) in rectal cancer to improve RT responses to immune checkpoint blockade: a trial to test the safety and efficacy of PD1 (AB122) and ADO dual receptor (AB928) antagonists with chemotherapy after short-course RT.[abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr P021

PD-1 cis-targeted IL-2v in combination with radiotherapy inhibits lung cancer growth and remodels the immune microenvironment

BackgroundMore efficient therapeutic options for non-small cell lung cancer (NSCLC) are needed as the survival at 5 years of metastatic disease is near zero. In this regard, we used a...

The Immune Contexture in Canine Anal Sac Adenocarcinoma: Immunohistochemical Quantification of Tumor-Infiltrating Lymphocytes and Tumor-Associated Macrophages with Image Analysis.

Canine anal sac gland adenocarcinomas (ASACs) are locally aggressive and highly metastatic to regional lymph nodes. Tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs) can be effective prognostic and predictive markers in numerous human neoplasms and are increasingly investigated in dogs. The aim of this study was to characterize immune cells in canine ASACs and their relationship with tumor size, histologic metastatic status, and tumor clinical stage. Thirty ASACs with known tumor size, metastatic status, and clinical stage were immunolabeled for Iba1 (macrophages), CD20 (B cells), CD3 (T cells), and Foxp3 (regulatory T cells). With image analysis, two areas of 1 mm2 were analyzed for each case at the tumor core (TC) and invasive margin (IM) and immune cells were counted. Eighteen patients had metastasis at the time of diagnosis, of which fifteen were nodal only, and three were both distant and nodal. The median tumor size was 32.5 mm (range 11-70). The clinical stage was I in five cases, II in seven cases, III in fifteen cases, and IV in three cases. T cells and macrophages were the most abundant immune cells in all tumors. Tumor size did not influence the number or type of infiltrating immune cells. By contrast, significantly higher numbers of TC T lymphocytes were found in patients without metastasis, while significantly higher numbers of TC macrophages were found in dogs with metastasis. Immune cell infiltrate did not differ according to clinical stage. The results indicate that the tumor immune microenvironment, specifically TILs and TAMs, contribute to tumor behavior and may influence metastatic potential; in particular, high CD3 infiltration may prevent tumor progression, while increased macrophage infiltration could promote it.

Immune landscape of the tumour microenvironment in Ethiopian breast cancer patients

BackgroundThe clinical management of breast cancer (BC) is mainly based on the assessment of receptor expression by tumour cells. However, there is still an unmet need for novel biomarkers important for prognosis and therapy. The tumour immune microenvironment (TIME) is thought to play a key role in prognosis and therapy selection, therefore this study aimed to describe the TIME in Ethiopian BC patients.MethodsRNA was isolated from formalin-fixed paraffin-embedded (FFPE) tissue from 82 women with BC. Expression of PAM50 and 54 immune genes was analysed using the Nanostring platform and differentially expressed genes (DEGs) were determined using ROSALIND®. The abundance of different cell populations was estimated using Nanostring’s cell type profiling module, while tumour infiltrating lymphocytes (TILs) were analysed using haematoxylin and eosin (H&E) staining. In addition, the PIK3CA gene was genotyped for three hotspot mutations using qPCR. Kaplan-Meier survival analysis and log-rank test were performed to compare the prognostic relevance of immune subgroups.ResultsFour discrete immune phenotypes (IP1-4) were identified through hierarchical clustering of immune gene expression data. These IPs were characterized by DEGs associated with both immune activation and inhibition as well as variations in the extent of immune infiltration. However, there were no significant differences regarding PIK3CA mutations between the IPs. A downregulation of immune suppressive and activating genes and the lowest number of infiltrating immune cells were found in IP2, which was associated with luminal tumours. In contrast, IP4 displayed an active TME chracterized by an upregulation of cytotoxic genes and the highest density of immune cell infiltrations, independent of the specific intrinsic subtype. IP1 and IP3 exhibited intermediate characteristics. The IPs had a prognostic relevance and patients with an active TME had improved overall survival compared to IPs with a significant downregulation of the majority of immune genes.ConclusionImmune gene expression profiling identified four distinct immune contextures of the TME with unique gene expression patterns and immune infiltration. The classification into distinct immune subgroups may provide important information regarding prognosis and the selection of patients undergoing conventional treatments or immunotherapies.

Immunotherapy in Oral Cancer

Abstract Squamous cell carcinoma of the head-and-neck (HNSCC) ranks sixth in global cancer incidence and poses significant challenges in terms of morbidity and mortality. The tumor microenvironment in HNSCC is a complex milieu involving immune cells, stromal elements, and cytokines, among other factors. Immunotherapy has emerged as a potent therapeutic avenue, particularly through immune checkpoint inhibitors (ICIs), for modulating this intricate environment. ICIs have garnered approval for first-line use in recurrent and metastatic HNSCC. However, recent clinical observations underscore the variability in treatment response to immunotherapy. This necessitates a thorough exploration of diverse ICI agents and combination strategies to optimize therapeutic outcomes. A comprehensive assessment and focused investigation of the immune contexture in HNSCC patients undergoing ICI therapy are pivotal for advancing treatment efficacy. Numerous innovative immunotherapeutic modalities, including chimeric antigen receptor-T-cell therapy, oncolytic virus therapy, and vaccination strategies, are actively under development. Furthermore, identifying robust biomarkers to guide patient selection for immunotherapy is of paramount importance. The quest for optimal combination regimens incorporating novel immunotherapies represents a recent paradigm shift in the management of HNSCC. This review is a concise summary of the clinical progress and ongoing trials in immunotherapy for HNSCC, highlighting the dynamic landscape of treatment approaches in this challenging disease context.

Method Development for Sorting Immune Cell Populations Within Tertiary Lymphoid Structures.

The tumor microenvironment is a complex network of interacting cells composed of immune and nonimmune cells. It has been reported that the composition of the immune contexture has a significant impact on tumor growth and patient survival in different solid tumors. For instance, we and other groups have previously demonstrated that a strong infiltration of T-helper type 1 (Th1), memory CD8+ T cells, and immune cells organized into tertiary lymphoid structures is associated with the long-term survival of cancer patients. Nevertheless, the prognostic value of the other immune populations, namely regulatory T cells (Treg), B cells, and gamma-delta (γδ) T cells remains a matter of debate. Herein, we describe novel flow cytometry-based strategies to sort out these different immune populations to evaluate their role in non-small-cell lung cancer (NSCLC).

Enhancing Anti-PD-1 Immunotherapy by Targeting MDSCs via Hepatic Arterial Infusion in Breast Cancer Liver Metastases.

Surgery, chemotherapy, and radiation often have limited utility for advanced metastatic disease in the liver, and despite its promising activity in select cancers, PD-1 blockade therapy similarly has minimal benefit in this setting. Curaxin, CBL0137, is an experimental anti-cancer drug that disrupts the binding of DNA to histones, destabilizes chromatin, and induces Z-DNA formation which may stimulate anti-tumor immune responses. Murine cell lines of colon (CT26) and breast (4T1) cancer were interrogated for survival and CBL0137-associated DNA changes in vitro. Immunocompetent models of liver metastases followed by CBL0137 hepatic arterial infusion (HAI) were used to examine in vivo tumor cell DNA alterations, treatment responses, and the immune contexture associated with CBL0137, both alone and in combination with anti-PD-1 therapy. CBL0137 induced immediate changes to favor tumor cell death in vitro and in vivo with an efficient tumor uptake via the HAI route. Toxicity to CBL0137 was minimal and anti-tumor treatment effects were more efficient with HAI compared to intravenous delivery. Immune effects were pronounced with CBL0137 HAI with concurrent depletion of a specific population of myeloid-derived suppressor cells and maintenance of effector T cell populations. Combination of CBL0137 HAI with PD-1 blockade improved survival in 4T1 tumors but not in CT26 tumors, and therapeutic efficacy relies on the finding of simultaneous and targeted depletion of myeloid-derived suppressor cells and skewing of T cell populations to produce synergy with PD-1 blockade therapy.

Roles of Chemokine Axes in Breast Cancer.

Chemokines bind to specific chemokine receptors, known as cell surface G protein-coupled receptors, constructing chemokine axes which lead to cell migration and invasion in developmental stage, pathophysiological process, and immune reactions. The chemokine axes in the tumor microenvironment are involved in tumor growth, angiogenesis, cancer stem-like cell properties, metastasis, and chemoresistance, modifying tumor immune contexture and cancer progression. Clinical features, including tumor state, grade, lymph node metastasis, and cancer subtypes, are related to the specific chemokine axes, which play a significant role in immune contexture and cell to cell interaction in the tumor microenvironment, followed by altered cancer prognosis and overall survival. The present review summarizes the role of chemokine axes in breast cancer, based on data obtained from cell line and animal models and human tumor samples. This review provides information that understand the important roles of each chemokine axis in breast cancer, probably offering a clue of adjuvant therapeutic options to improve the quality of life and survival for patients with breast cancer.

MA01.11 Unveiling Gene Expression and Immune Contexture in Stage II/III NSCLC Patients Receiving Neoadjuvant Pembrolizumab and Chemotherapy

MA01.11 Unveiling Gene Expression and Immune Contexture in Stage II/III NSCLC Patients Receiving Neoadjuvant Pembrolizumab and Chemotherapy

Robust estimation of cancer and immune cell-type proportions from bulk tumor ATAC-Seq data.

Assay for Transposase-Accessible Chromatin sequencing (ATAC-Seq) is a widely used technique to explore gene regulatory mechanisms. For most ATAC-Seq data from healthy and diseased tissues such as tumors, chromatin accessibility measurement represents a mixed signal from multiple cell types. In this work, we derive reliable chromatin accessibility marker peaks and reference profiles for most non-malignant cell types frequently observed in the microenvironment of human tumors. We then integrate these data into the EPIC deconvolution framework (Racle et al., 2017) to quantify cell-type heterogeneity in bulk ATAC-Seq data. Our EPIC-ATAC tool accurately predicts non-malignant and malignant cell fractions in tumor samples. When applied to a human breast cancer cohort, EPIC-ATAC accurately infers the immune contexture of the main breast cancer subtypes.

Robust estimation of cancer and immune cell-type proportions from bulk tumor ATAC-Seq data

Assay for Transposase-Accessible Chromatin sequencing (ATAC-Seq) is a widely used technique to explore gene regulatory mechanisms. For most ATAC-Seq data from healthy and diseased tissues such as tumors, chromatin accessibility measurement represents a mixed signal from multiple cell types. In this work, we derive reliable chromatin accessibility marker peaks and reference profiles for most non-malignant cell types frequently observed in the microenvironment of human tumors. We then integrate these data into the EPIC deconvolution framework (Racle et al., 2017) to quantify cell-type heterogeneity in bulk ATAC-Seq data. Our EPIC-ATAC tool accurately predicts non-malignant and malignant cell fractions in tumor samples. When applied to a human breast cancer cohort, EPIC-ATAC accurately infers the immune contexture of the main breast cancer subtypes.

EP.03B.02 Association of Pre-Existing Conditions with Major Driver Mutations and Immune Contextures in Non-Small Cell Lung Cancer

EP.03B.02 Association of Pre-Existing Conditions with Major Driver Mutations and Immune Contextures in Non-Small Cell Lung Cancer

SPI1+CD68+ macrophages as a biomarker for gastric cancer metastasis: a rationale for combined antiangiogenic and immunotherapy strategies

BackgroundTumor-associated macrophages (TAMs) have been demonstrated to be associated with tumor progression. However, the different subpopulations of TAMs and their roles in gastric cancer (GC) remain poorly understood. This study...

A Four-Gene Autophagy-Related Prognostic Model Signature and Its Association With Immune Phenotype in Lung Squamous Cell Carcinoma.

In the era of immunotherapy, there is a critical need for effective biomarkers to improve outcome prediction and guide treatment decisions for patients with lung squamous cell carcinoma (LUSC). We hypothesized that the immune contexture of LUSC may be influenced by tumor intrinsic events, such as autophagy. We aimed to develop an autophagy-related risk signature and assess its predictive value for immune phenotype. Expression profiles of autophagy-related genes (ARGs) in LUSC samples were obtained from the TCGA and GEO databases. Survival analyses were conducted to identify survival-related ARGs and construct a risk signature using the Random Forest algorithm. Four ARGs (CFLAR, RGS19, PINK1, and CTSD) with the most significant prognostic value were selected to construct the risk signature. Patients in the high-risk group exhibited worse prognosis than those in the low-risk group (p < 0.0001 in TCGA; p < 0.01 in GEO) and the risk score was identified as an independent prognostic factor. We observed that the high-risk group displayed an immune-suppressive status and showed higher levels of infiltrating regulatory T cells and macrophages, which are associated with poorer outcomes. Additionally, the risk score exhibited a significantly positive correlation with the expression of PD-1 and CTLA4, as well as the estimate score and immune score. This study provided an effective autophagy-related prognostic signature, which could also predict the immune phenotype.

The impact of preoperative treatments on the immune environment of rectal cancer.

To improve local disease control, the use of preoperative radiotherapy either alone or combined with chemotherapy has become standard practice in rectal cancer, but it is unclear how these treatments modify the antitumoral immune response. We aimed to evaluate tumor histopathologic features and the prognostic effect of host immune response in rectal cancer with variable treatment modalities. Ninety-five rectal cancers with short-course radiotherapy (SRT), 97 with long-course chemoradiotherapy (CRT), and 154 without preoperative treatments, were evaluated for histopathologic features including Crohn's-like reaction (CLR). CD3+ and CD8+ immunohistochemistry and tumor cells were analyzed from tumor tissue microarray samples to calculate T-cell densities and G-cross function values to estimate cancer cell-T-cell co-localization (proximity score). We found that lymphocyte densities were diminished after SRT, but CLR was scarcer after CRT. Proximity score and CLR density were prognostic for survival in cancer without preoperative treatments and could be combined into an enhanced prognostic score (immune grade). In the irradiated tumors, CLR density remained prognostic while the impact of T-cell infiltration was insufficient alone. In multivariable analysis, the immune grade proved to be an independent prognostic factor for survival. In conclusion, the immune contexture of rectal cancer harbors prognostic significance even after preoperative radiotherapy.

1916P Methylation subtypes correlate with tumor immune contextures and outcome to ICI therapy of pleural mesothelioma (PM) patients: The NIBIT EPI-MESO study

1916P Methylation subtypes correlate with tumor immune contextures and outcome to ICI therapy of pleural mesothelioma (PM) patients: The NIBIT EPI-MESO study