PD-L1 expression + MSI-H/dMMR

MSI-H status was associated with a higher TMB value and more positive PD-L1 expression in CCA tumors. Moreover, in patients with advanced CCA who received PD-1 inhibitor-based immunotherapy, MSI-H and positive PD-L1 expression were associated with improved both OS and PFS.

In this study, the prevalence of MSI-H phenotype is approximately 8.5% of unselected GCs. Approximately 76% of patients with MSI-H tumors showed PD-L1 expression with at least 1 CPS, and 50% revealed PD-L1 expression with at least 10 CPS, who can respond better to immune checkpoint inhibitors with promising therapeutic benefits. Due to the peritumoral expression of immune cells in PD-L1 positive GCs with MSI-H phenotype, different endoscopic approaches to obtain tumor tissues for PD-L1 evaluation would be considered, such as sampling tissues at the tumor periphery.

Background Given the early promising data with afatinib in advanced UC and the recent approval in NSCLC for anti-HER2 targeted therapy for activating kinase domain exon 20 ERBB2 insertion mutations, there is considerable interest in targeting additional locations in the ERBB2 gene in other tumor types...Conclusions ERBB2 ECD mutation-driven UBC represents a distinct subtype of UBC featuring an enrichment of MPUC histology from 1-2% to 28% incidence in ERBB2 ECD mutated UBC, and unique clinical and molecular characteristics, including differences in mutational signatures and genetic ancestry. Further exploration of anti-HER2 targeted therapy for non-amp sequence mutations in ERBB2 in UBC appears warranted.

Taken together, these results suggested that KMT2C/D LOF variants could be a useful predictor for ICIs efficacy in colorectal cancer. Meanwhile, the predictive value of KMT2C/D LOF variants was consistent with their association with TILs levels.

"While there were no differences in OS between CCNE1-amp vs non-amp GA, CCNE1Amp was associated with worse OS after trastuzumab in the IHC HER2+ cohort (N=9 vs 28; HR (95% CI): 2.95 (1.18 – 7.34), p = 0.015)...CCNE1Amp is associated with a distinct molecular profile in EGC and resistance to HER2-targeted therapy. While CCNE1-amp tumors are thought to be generally “immune-cold,”CCNE1-amp GA demonstrated potentially improved outcomes with immunotherapy. Further investigation of CCNE1Amp as a predictive biomarker is warranted, particularly as novel therapeutics selectively targeting CCNE1Amp are under clinical investigation."