PD-1 Inhibitors Research Articles

46P The comparison outcome of GEMOX and PD-1 inhibitors combined with or without lenvatinib for advanced intrahepatic cholangiocarcinoma (ICC): A prospective, single-center, open-label, double-arm phase II trial

46P The comparison outcome of GEMOX and PD-1 inhibitors combined with or without lenvatinib for advanced intrahepatic cholangiocarcinoma (ICC): A prospective, single-center, open-label, double-arm phase II trial

53054 PD-1 Inhibitor Use for Skin Malignancies in Patients with Solid Organ and Bone Marrow Transplants: Graft Rejection, Treatment Responses, and Survival

53054 PD-1 Inhibitor Use for Skin Malignancies in Patients with Solid Organ and Bone Marrow Transplants: Graft Rejection, Treatment Responses, and Survival

Low-dose apatinib optimizes the vascular normalization and enhances the antitumor effect of PD-1 inhibitor in gastric cancer.

Apatinib is a tyrosine kinase inhibitor that has shown potential in combination with immune checkpoint inhibitors (ICIs) in gastric cancer (GC); however, its role in GC is unclear. This research aims to investigate the effect of low-dose apatinib in GC, and analyze the mechanisms of its underlying action. A mouse model of GC was established, and the experimental mice were divided into different groups for different treatment: group NS (normal saline), group A (low-dose apatinib 50 mg/kg), group B (high-dose apatinib 200 mg/kg), group C [programmed cell death protein 1 (PD-1) inhibitor monotherapy], and group D (PD-1 inhibitor combined with low-dose apatinib). After 14 days of treatment, the tumor and blood samples were collected from all mice for histological and cytokine detection. Compared with the control group, mice in the low-dose apatinib group showed smaller tumor volumes and slower growth. CD31/α-smooth muscle actin (α-SMA) double staining revealed significantly higher coverage of perivascular cells in the low-dose apatinib group by contrast to the control and high-dose apatinib groups, suggesting that low-dose apatinib may alleviate hypoxia. Compared to the high-dose apatinib group, the expression of hypoxia inducible factor 1 alpha (HIF1α) significantly decreased in the low-dose apatinib group. Hematoxylin and eosin (HE) staining results showed a higher proportion of necrotic tumor tissues in the group of mice treated with low-dose apatinib combined with PD-1 inhibitor than in other groups. In addition, this combined treatment significantly reduced the expression of NG2 and HIF1α in mouse tumor tissues, indicating a more normalized vascular density, and also increased the proportion of CD8+ T cells. Low-dose apatinib enhances the antitumor effect of PD-1 inhibitor by normalizing tumor-related blood vessels, alleviating intratumor hypoxia and altering immunosuppressive microenvironment (IM).

Tumor perfusion enhancement by focus ultrasound-induced blood-brain barrier opening to potentiate anti-PD-1 immunotherapy of glioma

ObjectiveTo demonstrate the feasibility of using focused ultrasound to enhance delivery of PD-1 inhibitors in glioma rats and determine if such an approach increases treatment efficacy. MethodsC6 glioma in situ rat model was used in this study. Transcranial irradiation with FUS combined with microbubbles was administered to open the blood-brain barrier (BBB). The efficacy of BBB opening was evaluated in normal rats. The rats with glioma were grouped to evaluate the role of PD-1 inhibitors combined with FUS-induced immune responses in suppressing glioma when the BBB opens. Flow cytometry was used to examine the changes of immune cell populations of lymphocytes in peripheral blood, tumor tissue and spleen tissue of the rats. A section of rat brain tissue was also used for histological and immunohistochemical analysis. The survival of the rats was then monitored; the tumor progression and changes in blood perfusion of tumor were dynamically observed in vivo using multimodal MRI. ResultsFUS combined with microbubbles could enhance the blood perfusion of tumors by increasing the permeability of BBB (p < 0.0001), thus promoting the infiltration of CD4+ T lymphocytes (p < 0.01). Compared with the control group, the combination treatment group had increased in the infiltration number of CD4+(p < 0.05) and CD8+ T (p < 0.05); the tumor volume of the combined treatment group was smaller than that of the control group (p < 0.01) and the survival rate of the rats was prolonged (p < 0.05). ConclusionsIn this study, we demonstrated that the transient opening of the BBB induced by FUS enhanced tumor vascular perfusion and facilitated the delivery of PD-1 inhibitors, ultimately improving the therapeutic efficacy for glioblastoma.

The comparison of perioperative outcomes and disease-free survival between pneumonectomy after immunochemotherapy and after isolated chemotherapy: one single center experience

ObjectiveThis study aims to compare the perioperative outcomes and disease-free survival (DFS) between pneumonectomy after immunochemotherapy and chemotherapy.MethodsWe retrospectively identified patients who received neoadjuvant immunotherapy (n = 15) or chemotherapy alone (n = 12) in our single center between 2021 and 2023.The primary end point was 30-day major complications. The secondary end point was major pathologic response.ResultsThere was no significant difference in operation time, blood loss and postoperative stay time between ICI (Received immune checkpoint inhibitor treatment including PD-1 and PD-L1 inhibitors) and Chemo cohort. There were also no difference in postoperative complications including complications > grade III, 90-day death and bronchial fistula. The pCR rate was 40.0% (6/15) in the ICI cohort versus 0.0% (0/12) in the chemo cohort (p = 0.020). The MPR or pCR rate was 60.0% (9/15) in the ICI cohort versus 8.3% (1/12) in the chemo cohort (p = 0.014). ICI cohort was associated with an improved overall 1, 2, and 3-year disease-free survival(DFS)compared with chemo cohort. At the same time, both patients received ICI and Chemo were grouped according to whether pCR occurred or not, and it was found that DFS in the pCR group was better than DFS in the non-pCR group.ConclusionsBased on our results, we argue that compared with pneumonectomy after isolated chemotherapy, pneumonectomy after immunochemotherapy not added 90-day mortality, postoperative, morbidity, but improved DFS; thus, it should be the induction therapy choice for anatomically eligible centrally located lung cancers.

The KEYVIBE program: vibostolimab and pembrolizumab for the treatment of advanced malignancies.

Vibostolimab, a humanized IgG1 monoclonal antibody, blocks the interaction between TIGITand its ligands, preventing the immunosuppressive effects of TIGIT. The addition of vibostolimab to the PD-1 inhibitor pembrolizumab has shown promising antitumor activity, warranting further exploration of vibostolimab as a potential therapeutic option. The KEYVIBE program consists of nine trials that will evaluate the safety and efficacy of vibostolimab monotherapy and vibostolimab-based combination therapy in advanced solid tumors and hematological malignancies. These studies will also evaluate coformulated immunotherapy addressing issues that occur with the sequential administration of immunotherapy. The KEYVIBE program will provide further insight into the clinical utility of vibostolimab-based therapy across multiple indications and various stages of disease.

PD-1 inhibitor combined with SBRT, GM-CSF, and thymosin alpha-1 in metastatic breast cancer: A case report and literature review.

Triple-negative breast cancer is characterized by a worse prognosis compared with other breast cancer subtypes, especially in the case of pretreated metastatic triple-negative breast cancer (mTNBC). Because of the limited treatment options and suboptimal response rates, there is a pressing need to explore novel treatment protocols. A 48-year-old female patient diagnosed with mTNBC who had not responded to multiple lines of therapy (including surgery, chemotherapy, and radiotherapy) but demonstrated significant efficacy and abscopal effects after enrolling in our clinical trial. Triple-negative breast cancer with lung metastases. The clinical trial combined stereotactic body radiotherapy, immunotherapy, granulocyte-macrophage colony-stimulating factor, and thymosin alpha-1 to treat previously treated metastatic solid cancers. This combined treatment regimen implemented in this clinical trial yielded the patient's notable efficacy, accompanied by abscopal effects. The target lesion and the 3 observed lesions achieved a partial response according to the RECIST v1.1 criteria. reevaluation scans after 2 cycles of immunotherapy indicated a regression rate of -78.97% for the target lesion and -56.73% for the observed lesions. Hematological indexes were stable, and there was no apparent myelosuppression. Also, the tumor marker CA-199 exhibited a downward trend. During the course of treatment, the patient experienced a grade 2 skin reaction, which improved after receiving antiallergic treatment. No further adverse effects were observed. This treatment regimen may offer a promising treatment strategy for patients with mTNBC and other metastatic solid cancers.

The safety and efficacy of neoadjuvant PD-1 inhibitor plus chemotherapy for patients with locally advanced gastric cancer: A systematic review and meta-analysis.

The extensive utilization of immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 (PD-1) has achieved significant advancements in the treatment of diverse solid tumors. The present meta-analysis aims to evaluate the safety and efficacy of neoadjuvant chemotherapy (NCT) plus PD-1 inhibitor for patients with locally advanced gastric cancer (LAGC). An electronic search of PubMed, EmBase, and the Cochrane Library was performed to identify the clinical trials of NCT + PD-1 inhibitor vs. NCT in patients with LAGC. The retrieval period extended from the establishment of the corresponding database until April 2024, and meta-analysis was conducted using Stata (version 15) software. Subsequently, direct comparative analysis was used to compare pooled results of neoadjuvant immunochemotherapy (NICT) with NCT. After screening, 6 phase II/III randomized controlled trials (RCTs) and 9 retrospective studies with 2,953 patients were included. In meta-analysis, NICT group demonstrated a significantly higher rate of pathological complete response (pCR) (P<0.001) and R0 resection (P=0.001), and a lower 2-year recurrence rate (P=0.001) compared to the NCT group. The NICT group, however, exhibited a higher incidence of severe treatment-related adverse events (TRAEs) (P=0.044). Additionally, the NICT and NCT groups exhibited no statistical differences in terms of the number of harvested lymph nodes, the occurrence of total TRAEs and postoperative complications, as well as the duration of postoperative hospitalization. The combination of PD-1 inhibitor + NCT in LAGC patients enhances the likelihood of achieving radical surgery and improves prognosis, albeit to some extent increasing the risk of severe TRAEs. NICT is anticipated to emerge as the preferred neoadjuvant therapy option for patients diagnosed with LAGC.

Efficacy of PD-1 or PD-L1 inhibitors for the therapy of cervical cancer with varying PD-L1 expression levels: a single-arm meta-analysis.

To assess the effectiveness and tolerability of both PD-1 and PD-L1 inhibitors in advanced cervical cancer (CC), focusing on varying PD-L1 levels. A comprehensive exploration was carried out on EMBASE, PubMed, Cochrane Library databases as well as Web of Science up to May 25, 2024, for studies involving advanced CC patients receiving PD-1/PD-L1 inhibitors. Inclusion criteria were studies reporting objective response rate (ORR), disease control rate (DCR), median progression-free survival (PFS), as well as median overall survival (OS). Data extraction and quality assessment were performed by two reviewers using the JBI Case Series Critical Appraisal Checklist, followed by a meta-analysis via STATA/MP 16.0. Five eligible studies comprising 223 patients were chosen. ORR and DCR were 42% (95% CI: 17%-66%, P = 0.00) and 70% (95% CI: 22%-117%, P = 0.00), respectively, in the PD-L1 positive patients and were 36% (95% CI: 17%-54%, P = 0.00) and 47% (95% CI: 30%-63%, P = 0.00), respectively, in patients with PD-L1 negativity. For patients exhibiting PD-L1 positivity, median PFS and median OS were 3.98 months (95% CI: 0.80-7.16, P = 0.01) and 11.26 months (95% CI: 3.01-12.58, P = 0.00), respectively. With PD-1/PD-L1 inhibitors, PD-L1 positive CC patients demonstrate superior ORR, DCR, median PFS, and median OS, underscoring PD-L1 as one biomarker for immunotherapy response.

Matching-Adjusted Indirect Comparison of the Efficacy and Safety of Erdafitinib vs Enfortumab Vedotin in Patients with Locally Advanced Metastatic Urothelial Carcinoma.

Background: For patients with locally advanced or metastatic urothelial carcinoma (la/mUC), prognosis is poor and effective treatment options are limited. Erdafitinib is an oral fibroblast growth factor receptor (FGFR) kinase inhibitor approved by the FDA for the treatment of adults with la/mUC harboring FGFR alterations whose disease progressed following at least 1 prior line of therapy, including a PD-1 or PD-L(1) inhibitor, based on the phase 3, randomized THOR trial (NCT03390504, Cohort 1). Objective: To compare the efficacy and safety of erdafitinib vs enfortumab vedotin-ejfv (EV) in the absence of head-to-head comparison via an anchored matching-adjusted indirect comparison (MAIC). Methods: An anchored MAIC was conducted according to the National Institute for Health and Care Excellence Decision Support Unit guidance, with physician's choice of chemotherapy (docetaxel/paclitaxel and vinflunine) as the common comparator. Individual patient data from THOR were adjusted to match published key eligibility criteria and average baseline characteristics of EV-301, such as Bellmunt risk score, liver or visceral metastases, primary site, among others. Erdafitinib was then indirectly compared with EV using the relative treatment effects for the reweighted THOR population and those published for EV-301. Results: After matching, the effective sample size for THOR was 126 patients. The MAIC-recalculated hazard ratio (95% credible interval) for erdafitinib vs EV was 0.92 (0.54, 1.57) for overall survival and 0.93 (0.55, 1.56) for progression-free survival, yielding Bayesian probabilities of erdafitinib being better than EV of 62.1% and 60.5%, respectively. For response outcomes, the MAIC-recalculated risk ratio was 1.49 (0.56, 3.90) for confirmed objective response rate and 2.89 (0.27, 30.33) for confirmed complete response with probabilities of 72.6% and 81.3% for erdafitinib being better than EV, respectively. For safety, MAIC-yielded risk ratios of 1.09 (0.99, 1.21) for any treatment-related adverse events, 0.86 (0.57, 1.28) for grade 3+ TRAEs, and 1.02 (0.98, 1.06) for any treatment-emergent adverse events. Conclusion: The MAIC indicates comparable efficacy of erdafitinib vs EV for overall survival and progression-free survival, with erdafitinib showing a higher probability of achieving deep responses. While erdafitinib is associated with slightly more adverse events compared with EV, these events seem to be less severe.

Matching-Adjusted Indirect Comparison of the Efficacy and Safety of Erdafitinib vs Enfortumab Vedotin in Patients with Locally Advanced Metastatic Urothelial Carcinoma

Background: For patients with locally advanced or metastatic urothelial carcinoma (la/mUC), prognosis is poor and effective treatment options are limited. Erdafitinib is an oral fibroblast growth factor receptor (FGFR) kinase inhibitor approved by the FDA for the treatment of adults with la/mUC harboring FGFR alterations whose disease progressed following at least 1 prior line of therapy, including a PD-1 or PD-L(1) inhibitor, based on the phase 3, randomized THOR trial (NCT03390504, Cohort 1). Objective: To compare the efficacy and safety of erdafitinib vs enfortumab vedotin-ejfv (EV) in the absence of head-to-head comparison via an anchored matching-adjusted indirect comparison (MAIC). Methods: An anchored MAIC was conducted according to the National Institute for Health and Care Excellence Decision Support Unit guidance, with physician’s choice of chemotherapy (docetaxel/paclitaxel and vinflunine) as the common comparator. Individual patient data from THOR were adjusted to match published key eligibility criteria and average baseline characteristics of EV-301, such as Bellmunt risk score, liver or visceral metastases, primary site, among others. Erdafitinib was then indirectly compared with EV using the relative treatment effects for the reweighted THOR population and those published for EV-301. Results: After matching, the effective sample size for THOR was 126 patients. The MAIC-recalculated hazard ratio (95% credible interval) for erdafitinib vs EV was 0.92 (0.54, 1.57) for overall survival and 0.93 (0.55, 1.56) for progression-free survival, yielding Bayesian probabilities of erdafitinib being better than EV of 62.1% and 60.5%, respectively. For response outcomes, the MAIC-recalculated risk ratio was 1.49 (0.56, 3.90) for confirmed objective response rate and 2.89 (0.27, 30.33) for confirmed complete response with probabilities of 72.6% and 81.3% for erdafitinib being better than EV, respectively. For safety, MAIC-yielded risk ratios of 1.09 (0.99, 1.21) for any treatment-related adverse events, 0.86 (0.57, 1.28) for grade 3+ TRAEs, and 1.02 (0.98, 1.06) for any treatment-emergent adverse events. Conclusion: The MAIC indicates comparable efficacy of erdafitinib vs EV for overall survival and progression-free survival, with erdafitinib showing a higher probability of achieving deep responses. While erdafitinib is associated with slightly more adverse events compared with EV, these events seem to be less severe.

Review of T Helper 2-Type Inflammatory Diseases Following Immune Checkpoint Inhibitor Treatment.

Immune checkpoints are mechanisms that allow cancer cells to evade immune surveillance and avoid destruction by the body's immune system. Tumor cells exploit immune checkpoint proteins to inhibit T cell activation, thus enhancing their resistance to immune attacks. Immune checkpoint inhibitors, like nivolumab, work by reactivating these suppressed T cells to target cancer cells. However, this reactivation can disrupt immune balance and cause immune-related adverse events. This report presents a rare case of prurigo nodularis that developed six months after administering nivolumab for lung adenocarcinoma. While immune-related adverse events are commonly linked to T helper-1- or T helper-17-type inflammations, T helper-2-type inflammatory reactions, as observed in our case, are unusual. The PD-1-PD-L1 pathway is typically associated with T helper-1 and 17 responses, whereas the PD-1-PD-L2 pathway is linked to T helper-2 responses. Inhibition of PD-1 can enhance PD-L1 functions, potentially shifting the immune response towards T helper-1 and 17 types, but it may also influence T helper-2-type inflammation. This study reviews T helper-2-type inflammatory diseases emerging from immune checkpoint inhibitor treatment, highlighting the novelty of our findings.

Analysis of the Safety and Effectiveness of Lenvatinib + TACE-HAIC + PD-1 Inhibitor for Intermediate and Advanced Hepatocellular Carcinoma

Background: Hepatocellular carcinoma (HCC) is the sixth most prevalent cancer and the fourth leading cause of cancer death in the world. Aims: This study aimed to investigate the efficacy and safety of Lenvatinib + PD-1 inhibitor + TACEHAIC (LePTaHAIC) versus Sorafenib + TACE (SorTACE) for patients with intermediate and advanced HCC. Methods: In this retrospective study, patients diagnosed with BCLC stage B/C HCC were included. All patients were treated with LePTaHAIC (LePTaHAIC group) or SorTACE (SorTACE group) between September 2019 and September 2020. Outcomes, including progression-free survival (PFS), conversion surgical resection rate, objective remission rate (ORR), overall survival (OS), and treatment-related adverse events (AEs) were analyzed and compared between the two treatment modalities. Results: In total, 65 eligible patients were recruited, with 35 assigned to receive LePTaHAIC and 30 assigned to undergo SorTACE. Median PFS (11.4 vs. 5.13 months) and OS (26 vs. 10.08 months) in the LePTaHAIC group were significantly higher compared to the SorTACE group (both P &lt; 0.0001). The ORR (mRECIST standard) of the LePTaHAIC group was markedly higher compared to the SorTACE group (71.4% vs. 40%, P = 0.01). In the LePTaHAIC group, 11 patients underwent surgical resection (BCLC stage B: n = 4, BCLC stage C: n = 7) and 3 patients achieved complete pathological remission (pCR), while one patient in the SorTACE group underwent surgical resection. The conversion surgical resection rate of the LePTaHAIC group was significantly higher compared to the SorTACE group [31.4% (11/35) vs. 3.3% (1/30), P = 0.004]. Patients with LePTaHAIC had more frequent grade 3-4 treatmentrelated AEs, especially thrombocytopenia, compared to the SorTACE group (22.9% vs. 3.3%, P = 0.02). Conclusion: LePTaHAIC exhibited acceptable toxic effects and improved survival compared to SorTACE in intermediate and advanced HCC.

Changes in systemic immune-inflammation index (SII) predict the prognosis of patients with hepatitis B-related hepatocellular carcinoma treated with lenvatinib plus PD-1 inhibitors.

This study aimed to evaluate the prognostic significance of changes in inflammatory markers in patients with Hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) treated with first-line lenvatinib plus a programmed cell death protein 1 (PD-1) inhibitor. This study retrospectively included 117 HBV-HCC patients treated with first-line lenvatinib in combination with a PD-1 inhibitor. Independent factors affecting progression-free survival (PFS) and overall survival (OS) were explored based on baseline indicators and inflammatory markers changes after one treatment cycle. Multivariate analysis revealed that an alpha-fetoprotein (AFP) level 400 ng/mL [hazard ratio (HR), 1.69; 95% confidence interval (CI), 1.11-2.58; P = 0.01] was identified as an independent risk factor, platelet-to-neutrophil ratio (PNR) 65.43 (HR 0.50; 95% CI 0.30-0.84; P and SII 539.47 (HR 0.54; 95% CI 0.30-0.96; P = 0.03) were identified as independent protective factors for PFS. Additionally, multivariate analysis demonstrated that AFP 400 ng/mL, HBV-HCC patients with diabetes mellitus (DM), and SII were independent risk factors of OS. The patients whose SII had increased after one cycle of treatment showed a poorer PFS (HR 1.61; 95 %CI 1.10-2.37; P = 0.015) and OS (HR 1.76; 95 % CI 1.15-2.70; P = 0.009) than patients whose SII had decreased. The objective response rate (ORR) was higher in the SII-decreased patients (47.5% vs 32.5%, P = 0.11). Mann-Whitney test found a significant difference in therapeutic response between the SII-increased patients and the SII-decreased patients (P = 0.04). SII can be associated with outcomes in patients with HBV-HCC treated with first-line lenvatinib plus PD-1 inhibitors.

Clinical and Pathologic Response to Neoadjuvant Immunotherapy in DNA Mismatch Repair Protein-Deficient Gastroesophageal Cancers.

Mismatch repair deficient (dMMR) gastroesophageal cancers (GEC) are a distinct subgroup. Among patients with locally advanced disease, previous trial data suggest a good response to neoadjuvant immune checkpoint inhibitors (nICI). Since 2019, our institution has routinely performed MMR testing for new GEC cases. Patients diagnosed with GEC (2019-2024) were included in the study. Quantitative data are described as the median and interquartile range (IQR); qualitative data are described as quantities and percentages. A total of 24 patients with dMMR GEC were identified following implementation of routine immunohistochemical testing; 14 were potentially resectable with a median follow-up of 14 months (IQR 8-27). All patients underwent pre-treatment positron emission tomography (PET; median SUV 20.9). Among the 14 potentially resectable patients, 4 underwent immediate surgery, 10 were treated with nICI, and 5 underwent surgical resection to date. All regimens included PD-1 inhibitors, with 70% receiving pembrolizumab. Re-staging PET was performed in five patients; the median post-nICI SUV was 5.1 (range 4.7-6.3). All resected specimens had gross ulceration after nICI, but 60% (N = 3) had a pathologic complete response (pCR) following nICI; one patient had a near-complete response (nCR) and one patient had a partial response (pPR). Reduction in SUV was 75% and 82% in the pCR patients, 25% in the nCR patient, and 43% in the pPR patient. dMMR GECs are responsive to nICI in this limited experience, mirroring early clinical trial data. Given persistent metabolic activity and visible ulceration despite pCR, studies should continue to optimize tools for estimating post-nICI pCR in these patients.

Morphological and Immunohistochemical Aspects with Prognostic Implications and Therapeutic Targets of Primary Sinonasal Mucosal Melanoma: A Retrospective Study.

Sinonasal mucosal melanoma originates from melanocytes and it is a rare malignancy in the sinonasal tract. It is an aggressive melanocytic neoplasm with a very poor prognosis. The symptoms are nonspecific and the diagnosis is delayed, usually until the advanced stages of the disease. The current study performs a correlation between the histopathological aspects of sinonasal mucosal melanoma and different types of immune cells present in the microenvironment, with prognostic and therapeutic implications. The endpoint is to quantify the cellular immune microenvironment and correlate it with patient survival. This study presents nine cases of primary sinonasal mucosal melanomas diagnosed at the Emergency City Hospital Timisoara, Romania during a period of 15 years. The histopathological examination was performed in the Department of Pathology of the same hospital, using morphological hematoxylin-eosin staining. Additional immunohistochemical reactions were performed to confirm the diagnosis and evaluate the components of the tumor immune microenvironment. This study identifies eosinophils, macrophages, natural killer cells and plasma cells as favorable prognostic factors. Therefore, a CD8:CD4 ratio of more than 3 is correlated with a good response to PD-1 inhibitor therapy.

Prognostic value of a novel myeloid-to-lymphoid ratio biomarker in advanced gastric cancer.

Currently, immune checkpoint inhibitors (ICIs) have excellent performance in the clinical treatment of advanced gastric cancer (AGC). However, precisely selecting AGC patients who can benefit from immunotherapy is an urgent difficulty. In this study, we investigated the immunoprognostic role of myeloid-to-lymphocyte ratio (M:L) in AGC patients. We collected information on 268 AGC patients who were hospitalized in the Department of Medical Oncology of PLA General Hospital from December 2014 to May 2021. The patients were divided into low M: L group (< 3.76) and high M:L group (≥ 3.76). Survival differences between different M: L level groups at baseline and after treatment were analyzed by methods such as Kaplan-Meier, Cox or Logistic regression model. Progression free survival (PFS) (5.8months vs. 3.4months, p = 0.001) and overall survival (OS) (14.1months vs. 9.0months, p = 0.001) were significantly longer in the low M:L group than in the high M:L group. After analyses of Cox regression modeling it was concluded that M:L was an independent prognostic factor for PFS (HR 1.371 95%CI 1.057-1.777 p = 0.017) and OS (HR 1.352 95%CI 1.003-1.824 p = 0.048), respectively. Subsequent subgroup analyses performed across immunotherapy lines, regimens, PD-1 inhibitor agents, and age groups revealed a poorer prognosis in the high M:L group. Notably, an increase in the value of M:L after treatment significantly increased the risk of poor prognosis. M:L ≥ 3.76 is associated with poor prognostic outcomes in AGC patients receiving immunotherapy and may be a predictive biomarker of prognosis. This result needs to be confirmed by larger prospective studies.

Pembrolizumab plus cetuximab with neoadjuvant chemotherapy for head and neck squamous cell carcinoma.

Head and neck cancer cells commonly express programmed death ligand 1 (PD-L1) and epidermal growth factor receptor (EGFR), both of which play pivotal roles in the antitumor cellular immune response. Pembrolizumab, a PD-1 inhibitor, and cetuximab, an EGFR inhibitor, are typically effective agents combined with neoadjuvant platinum-based chemotherapy for the treatment of head and neck squamous cell carcinoma (HNSCC). This study aims to evaluate the efficacy and safety of neoadjuvant immunochemotherapy in patients with HNSCC. Patients with HNSCC underwent radical surgery and complete cervical lymph node dissection following neoadjuvant immunochemotherapy at RenJi Hospital from January 2021 to June 2024 were retrospectively analyzed. The primary endpoint was major pathological response (MPR). We further explored the relationship between the efficacy and immune estimators. Twenty-one patients were enrolled in this retrospective study. The MPR was 66.7%, including 11 patients who achieved a pathological complete response (pCR). The overall response rate (ORR) was 90.5%, and the complete response (CR) rate was 28.6%. The oropharynx, as the primary site, was the sensitive tumor type to neoadjuvant immunochemotherapy. The most common adverse event (AEs) was anemia (61.9%). No grade 4 AE or delayed surgery was reported. Laryngeal preservation rates were 90.9% (10/11), and pathological findings confirmed negative surgical margins for all patients. Moreover, pre-treatment peripheral lymphocyte count, monocyte count, and platelet to lymphocyte ratio (PLR) displayed a significant correlation with the treatment response. Pembrolizumab plus cetuximab with chemotherapy for patients with HNSCC is a feasible and safe clinical protocol fulfilling organ preservation and life quality improvement. Pre-treatment peripheral immune estimators could help to screen patients who may respond to the neoadjuvant immunochemotherapy.

Rhodium(III) Complex Noncanonically Potentiates Antitumor Immune Responses by Inhibiting Wnt/β-Catenin Signaling.

Metal-based chemoimmunotherapy has recently garnered significant attention for its capacity to stimulate tumor-specific immunity beyond direct cytotoxic effects. Such effects are usually caused by ICD via the activation of DAMP signals. However, metal complexes that can elicit antitumor immune responses other than ICD have not yet been described. Herein, we report that a rhodium complex (Rh-1) triggers potent antitumor immune responses by downregulating Wnt/β-catenin signaling with subsequent activation of T lymphocyte infiltration to the tumor site. The results of mechanistic experiments suggest that ROS accumulation following Rh-1 treatment is a critical trigger of a decrease in β-catenin and enhanced secretion of CCL4, a key mediator of T cell infiltration. Through these properties, Rh-1 exerts a synergistic effect in combination with PD-1 inhibitors against tumor growth in vivo. Taken together, our work describes a promising metal-based antitumor agent with a noncanonical mode of action to sensitize tumor tissues to ICB therapy.

Efficacy of immune checkpoint inhibitors combined with bevacizumab in MSS/pMMR advanced colorectal cancer after first-line treatment failure.

To investigate the effects of a PD-1 inhibitor combined with a bevacizumab monoclonal antibody on tumor immune cells in patients with first-line treatment failure in MSS/pMMR advanced colorectal cancer. Control group consisted of 50 patients treated with the FOLFIRI combined with Bevacizumab regimen. The experimental group consisted of 60 patients treated with the Sintilimab combined with Bevacizumab regimen. By comparing the expression levels of CD8+ T lymphocytes, TAMs, and CAFs before and after treatment, short-term efficacy after treatment, and adverse drug reactions between the two groups, we comprehensively evaluated the impact of Sintilimab combined with Bevacizumab on patients with MSS/pMMR advanced colorectal cancer who failed first-line treatment. There was a statistically significant difference in the percentage of CD8+ T lymphocytes, TAMs, and CAFs before and after treatment between the two groups (P<0.05);Immunohistochemical scoring of CD8+ T lymphocytes, TAMs, and CAFs showed significant differences between the groups post-treatment (P<0.05). The experimental group demonstrated statistically significant differences in immunohistochemical scoring of CD8+ T lymphocytes, TAMs, and CAFs before and after treatment (P<0.05). There was a statistically significant difference in the therapeutic effect between the two groups of tumors (P<0.05). The experimental group had greater PFS, mPFS, ORR, and DCR than did the control group. There was no statistically significant difference in the occurrence rate of drug-related adverse reactions after treatment between the two groups (P>0.05). The results of the Cox proportional hazards model analysis indicate that age, gender, and group are independent risk factors affecting MSS/pMMR advanced colorectal cancer patients treated with second-line therapy in this study. Patients aged ≤60 years, male patients, and those in the experimental group showed better treatment responses in this study. By administering immune checkpoint inhibitors in combination with bevacizumab to patients with advanced colorectal cancer with MSS/pMMR disease for whom first-line treatment failed, not only did the patients' prognosis improve, but the adverse drug reactions were also safe and controllable.