PD-L1-L

Renal malignant eAML also known as malignant PEComa of the kidney is an exceedingly rare tumor with propensity for malignant behavior that frequently displays a variety of germline mutations as well as GA indicative of potential efficacy of MTOR pathway inhibitors.

This study highlights the crucial link between RNA modification and TME diversity. Evaluating RNA modification in tumors improves our understanding of TME features and supports the development of effective immunotherapy strategies.

In this large, pooled nonrandomized retrospective analysis, we observed that NIVO + IPI provides longer OS than NIVO in patients with ICI treatment-naïve advanced melanoma and identifies clinical factors that appear to be associated with survival for each treatment, which may assist with treatment decision making.

BEMPEG plus NIVO did not meet the efficacy threshold for ORR in patients with previously untreated locally advanced or metastatic urothelial carcinoma and low PD-L1 expression.

HNSCC patients with BM frequently have oropharyngeal primary sites and are HPV+. Common molecular alterations in BM samples, including targetable PIK3CA and ATM, were identified. MAP2K2 alterations were enriched and densities of immune cells were low, highlighting potential targets for further research and immunotherapy considerations.

In PD-L1low HER-2 negative GEAC, the benefit of first-line ICI is modest, yet significant. Further translational work is warranted to better select patients who could benefit from immunotherapy in this setting. Meanwhile, alternative therapeutic options such as zolbetuximab in Claudin18.2-positive disease must be taken into account.

This preliminary study supports the use of AI algorithms for the scoring of PD-L1 and TILs in patients with NSCLC.

Background American Cancer Society estimates that 22,370 new cases of esophageal cancer were diagnosed in the United States in 2024.1 In March 2021, Pembrolizumab received FDA approval for use as monotherapy after one or more prior lines of systemic therapy for esophageal cancer patients with squamous cell histology that expresses PD-L1 (Combined Positive Score (CPS) ≥ 10) as determined by PD-L1 IHC 22C3 pharmDx...Conclusions This study demonstrates high reproducibility of PD-L1 IHC 22C3 pharmDx with respect to PD-L1 expression in esophageal cancer specimens at the CPS ≥ 1 cutoff. Ethics Approval The external reproducibility study was approved by WCG IRB, study numbers 1356915, 1357191, 1357539.

The KEYNOTE-B84 study (NCT04815720) evaluated the safety and efficacy of pepinemab in combination with pembrolizumab as a first-line treatment for immunotherapy-naïve patients with R/M HNSCC. Biomarker studies conducted in patients with surgically resectable metastatic melanoma (NCT03769155) and HNSCC (NCT03690986) received neoadjuvant treatment with pepinemab/nivolumab/ipilimumab combinations compared to nivolumab or ipilimumab alone...Increased density and maturity of lymphoid aggregates correlated with disease control and longer progression-free survival (PFS). Conclusions Pepinemab, a Semaphorin 4D (SEMA4D) blocking antibody, in combination with ICB converts 'Cold' tumors to 'Hot' by inducing organized lymphoid aggregates.

Efficacy for this combination at the RP2D was observed in tumors with low PD-L1 and was not dependent on FGFR3 gene alterations, suggesting broad potential benefit for patients with locally advanced/metastatic UC and FGFR mRNA overexpression. ClinicalTrials.gov Identifier: NCT03473756.

Screening and on-treatment tumor biopsies were collected from several clinical trials: the KEYNOTE-B84 study (NCT04815720), that evaluated the safety and efficacy of pepinemab in combination with pembrolizumab as a first-line treatment for immunotherapy-naïve patients with R/M HNSCC, and biomarker neoadjuvant studies conducted in metastatic melanoma (NCT03769155) and HNSCC (NCT03690986) patients with surgically resectable disease treated with pepinemab/nivolumab/ipilimumab combinations compared to nivolumab or ipilimumab alone. When SEMA4D is blocked from binding to its receptors, suppression is reduced, leading to increased penetration and organization of antigen presenting cells (APC) and lymphoid cells in the tumor microenvironment. It is expected that this would facilitate interaction and communication among these cell populations, accounting for improved immune responses in otherwise "cold" tumors.

In addition, a high ratio of CD8+ cells to M2 macrophages was found to predict favorable outcomes in patients with PD-L1-expressing lung cancer after immune checkpoint inhibitor therapy. This study demonstrates that TCs and ICs have distinct spatial features within the tumor microenvironment that are related to tumor PD-L1 expression and IC infiltration.