PD-L1 (Programmed death ligand 1)

Durvalumab + tremelimumab treatment resulted in meaningful responses in salivary carcinoma and CCCO and deserves further exploration in front-line studies. AstraZeneca and Canadian Cancer Society.

Together, these findings indicate the existence of a molecular context linking dedifferentiation and IFNγ signaling in melanoma which may lead to immune evasion. Additionally, the variability in PD-L1 expression among MITFlow and MITFhigh cells suggests that high IFNγ-induced PD-L1 expression associates with enhanced inflammatory gene expression. These results imply that modulating melanoma differentiation may help shape IFNγ responsiveness.

Targeting TM4SF1 via AAV induced tumor senescence, reduced tumor burden and synergistically enhanced the efficacy of anti-PD-1 therapy. Our results revealed that TM4SF1 regulated tumor cell senescence and immune evasion through the AKT pathway, highlighting its potential as a therapeutic target in HCC, particularly in combination with first-line immunotherapy.

Mechanistically, BPNS reduced PD-L1 expression through two main pathways: by inducing autophagy via binding to the HSP90 protein, leading to PD-L1 degradation through the autophagy pathway, and by inhibiting the PI3K-AKT signaling pathway, which reduced PD-L1 mRNA levels. This study expands the understanding of BPNS biological activity and suggests new strategies for utilizing BPNS as an adjuvant in immunotherapy.

TMIT I group within the NHPVA population is most likely to benefit from PD-L1/PD-1 blockade immunotherapies. The immune classification of ECA demonstrates significant prognostic value, suggesting its potential utility in guiding clinical stratification and therapeutic decision-making.

Among patients with metastatic NSCLC who are treated with pembrolizumab or chemoimmunotherapy, the presence of a pathogenic TP53 and KRAS mutation is associated with longer OS. Nevertheless, in multivariable Cox regression analysis including age, sex, clinical disease stage, and PD-L1 tumor proportion score, KRAS/TP53 mutation status was no longer associated with OS.

Moreover, the tumors of these patients presented high enrichment scores for NK cells, antitumor cytokines, and Th1 signatures, and a low enrichment score for cancer-associated fibroblasts. This study shows the molecular characteristics associated with the efficacy of pembrolizumab in BTC of the MSS type.

In breast cancer, hsa-miR-214-3p reduces tumor cell proliferation and enhances the tumor immune microenvironment by downregulating B7H3. These findings suggest new potential targets for the clinical treatment of breast cancer.

Several targeted therapies, including bevacizumab and sunitinib, have failed to demonstrate significant clinical benefit in TNBC...Pembrolizumab is approved for use in both early and advanced TNBC in combination with standard chemotherapy...In this review, we explore the challenges of immunotherapy in TNBC, examining the mechanisms of tumor progression mediated by immune cells within the tumor microenvironment, and the signaling pathways involved in both primary and acquired resistance. Finally, we provide a comprehensive overview of ongoing clinical trials underway to investigate novel immune-targeted therapies for TNBC.

Considering the variability in EGFR-mutant NSCLC, including expression levels of programmed cell death ligand 1 (PD-L1), tumor mutation burden (TMB), and other immunological features, the application of immunotherapy in this group is still a subject of investigation. Therefore, we have summarized and analyzed the immunological characteristics and regulatory mechanisms of different EGFR mutations in NSCLC, as well as the current clinical application of immunotherapy in the EGFR-mutant population, to provide a reference for future research.

A total of 8 RCTs meeting our eligibility criteria were included, involving 4626 patients who received either Paclitaxel (Paclitaxel-placebo/chemotherapy) or a combination of durvalumab, pembrolizumab, atezolizumab, toripalimab with paclitaxel. The combination of Durvalumab and paclitaxel represents the optimal treatment option. In the future, attention should be paid to the TNBC subtypes and drug dosage, as these factors may help to design personalized TNBC treatment programs.

LAG3 acts as an immunosuppressive molecule in breast cancer, inhibiting T CD8 + cell proliferation and cytokine production by T cells. We proposed the modulation of a novel checkpoint molecule, such as LAG3, as potential biomarkers associated to a rapid diagnosis.

High expression of PD-L1 and CD24 are risk factors for poor prognosis in HBV-associated HCC patients following curative resection. PD-L1 is significantly correlated with CD24 and CD47.

CHD1L also increased the relative protein expression of p-PI3K, p-AKT, and PD-L1 in A431 cells, as well as CD9, TSG101, PD-L1 in exosomes, CD206, Arginase-1, p-AKT, p-mTOR, VEGF, COX-2, MMP2, MMP9, and p-ERK1/2 in tumor-associated macrophages, while inhibiting the relative protein expression of iNOS and IL-1β. Under hypoxic conditions, CHD1L can promote the proliferation and migration of cutaneous squamous cell carcinoma.

These findings reveal actionable insights into targeted therapies, including immune checkpoint inhibitors and PARP inhibitors, which hold promise for improving outcomes in HGSOC. This synthesis of knowledge aims to bridge gaps in understanding HGSOC's multifaceted biology, enhance clinical decision-making, and foster the development of precision therapies.

We demonstrate that because of these changes, EVs derived from glioma cells lacking PTEN have a greater ability to suppress T cell receptor (TCR) signaling. Taken together, these findings provide important new insights into how the loss of PTEN can contribute to an immunosuppressive TIME, facilitate immune evasion, and highlight a novel role for PI3K signaling in the regulation of EV biogenesis and the cargo they contain.

To achieve this, the mitochondria-targeting triphenylphosphorus (TPP) was linked to photosensitizer Chlorin e6 (Ce6) to form TPP-Ce6 (TCe6), which was then self-assembled with copper ions and thymopentin (TP5) to obtain TCe6@Cu/TP5 NPs...Moreover, TP5 significantly promoted the proliferation and differentiation of dendritic cells (DCs) and T lymphocytes to further amplify the cancer immunity cycle. Collectively, our TCe6@Cu/TP5 NPs effectively facilitate drug accumulation and activate systemic antitumor immunity in vitro and in vivo, providing an innovative solution across the BBB that potentiates GBM immunotherapy.

PD-L1 expression with ≥ 10 CPS was observed in 21.2% of EBV-GCLSs, predominantly in MSI-H tumors (85.7%). EBV positivity and MSI are associated with PD-L1 positivity rates in patients with GCLS who may respond better to PD-1/PD-L1 inhibitors but not anti-HER2 inhibitors.

The expert working group also made recommendations for pre-analytic, analytic, and post-analytic considerations for predictive biomarker testing in G/GEJ adenocarcinoma. Implementation of these recommendations will provide medical oncologists with accurate, timely biomarker results to use for treatment decision-making.

The expression of PD-1 on TILs and PD-L1 on tumor cells correlated significantly with the grading of TILs in colorectal adenocarcinoma. This finding shows potential as a predictive biomarker for PD-1/PD-L1 blockade therapy. Further studies are needed to strengthen these results.

The confirmation of ERBB2 (HER2) amplification in the MPTT through a molecular analysis suggests potential therapeutic avenues involving anti-HER2 monoclonal antibodies. The presence of the TP53 mutation, without the concurrent gene mutations typically observed in SCC, significantly aided in this differential diagnosis.

P2/3, N=600, Recruiting, Exelixis | Trial completion date: Mar 2028 --> Mar 2029 | Trial primary completion date: Jun 2027 --> Aug 2028

P1/2, N=86, Recruiting, Vyriad, Inc. | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

P1, N=36, Active, not recruiting, Merck Sharp & Dohme LLC | Recruiting --> Active, not recruiting | Trial completion date: Jun 2025 --> Nov 2025 | Trial primary completion date: Jun 2025 --> Nov 2025

P3, N=580, Recruiting, Sun Yat-sen University

Moreover, females exhibited increased PD-L1 mRNA expression compared to males in the AD group, and PD-L1 mRNA levels were higher in females with right-sided CRC than in those with cancer at other locations. Differences in NRF2 and PD-L1 expression indicate site-specific colon carcinogenesis based on sex, particularly in females with right-sided CRC.

A strong relationship between cancer stemness and the response to immunotherapy has been identified in our study. This finding provides valuable insights for devising efficient strategies to address immune evasion by targeting the regulation of genes associated with cellular stemness.

Post-immunochemotherapy, CD8+ T cells increase, but CD38+CD8+ T cells show reduced functionality. These findings highlight the complex immune dynamics and their implications for NSCLC treatment.

Both interferon treatment and finite antiviral therapy have been found to be associated with positive HBV outcomes. Overall, combining immune checkpoint inhibitors with nucleos(t)ide analogs appears to be a promising approach for achieving HBsAg loss, particularly in patients with low HBsAg levels.

P2, N=400, Completed, Yonsei University | Active, not recruiting --> Completed | Trial completion date: Dec 2022 --> Mar 2024

P2, N=46, Active, not recruiting, Washington University School of Medicine | Trial completion date: Sep 2025 --> Sep 2026 | Trial primary completion date: Dec 2024 --> Dec 2025

TBLC was found to be a safe and effective diagnostic tool for peripheral lung cancer in elderly patients and provided adequate samples for molecular testing. Since the complication rates did not significantly differ between the two age groups, age alone should not be considered a contraindication for the procedure.

The present study indicated that uHDR C-ion has a different impact on the repair pathway of DNA damage and ER than the Conv C-ion. This is the first study to show the immune-related protein expressions on cancer cells after uHDR C-ion irradiation.

The findings of this cohort study demonstrate a strong and independent deep learning-based feature associated with ICI response in patients with NSCLC across various cohorts. Clinical use of this deep learning model could refine treatment precision and better identify patients who are likely to benefit from ICI for treatment of advanced NSCLC.

P1/2, N=314, Active, not recruiting, Hoffmann-La Roche | N=675 --> 314

P2, N=93, Active, not recruiting, Hoffmann-La Roche | Recruiting --> Active, not recruiting | Trial primary completion date: Oct 2025 --> May 2024

P2, N=17, Completed, Sunnybrook Health Sciences Centre | Unknown status --> Completed

P3, N=719, Completed, Bristol-Myers Squibb | Active, not recruiting --> Completed | Trial completion date: Jan 2026 --> Oct 2024

P1/2, N=156, Recruiting, Corbus Pharmaceuticals Inc. | Not yet recruiting --> Recruiting

The patient subsequently received chemotherapy with pemetrexed and carboplatin. This case offers a long-term follow-up of the effectiveness and safety of combining pembrolizumab and anlotinib in advanced SMARCA4-UT, and substantiates the role of long-term immunotherapy in preventing radiographic/clinical recurrence following surgery. This case illustrates new potential efficacy of immunotherapy in combination with surgery as a treatment approach of SMARCA4-UT.

Although pretreatment of pediatric sarcoma cell lines with TNF did not improve unspecific peripheral blood mononuclear cells (PBMCs) cytotoxicity, TNF enhanced specific lysis of 1/3 HLA-A2+ EwS cell lines by CHM1319 CD8+ T cells depending on MHC-I expression and ICAM-1 upregulation. Our study supports utilization of TNF or TNF-inducing regimens for upregulation of MHC-I and costimulatory surface molecules on pediatric sarcoma cells and for enhancing recognition of responsive HLA-A2+ EwS tumor cells by antigen-specific CD8+ T cells.

In our series, their prognostic value outperformed that of TILs. Therefore, their easy quantification on routine HES sections and their integration into the factors classically analyzed by pathologists could improve the clinical management of TNBC, a breast cancer type whose prognosis remains too poor.