Next generation sequencing-based MSI scoring predict benefit in mismatch repair deficient tumors treated with nivolumab: follow-up on NCI-MATCH arm Z1D.

Purpose: Mismatch repair deficient (dMMR) tumors have demonstrated favorable responses to immune checkpoint inhibition targeting PD-1. However, more in-depth identification of predictors of response could further refine patient selection for immunotherapy treatment.

Experimental Design: We undertook integrated evaluation performed on samples collected from 28 of 42 patients enrolled on the NCI-MATCH arm Z1D trial that evaluated PD-1 inhibition treatment with nivolumab in patients with non-colorectal dMMR tumors.

Tumor-derived CCL2 drives tumor growth and immunosuppression in IDH1- mutant cholangiocarcinoma.

Background And Aims: Isocitrate dehydrogenase 1 ( IDH1 )-mutant cholangiocarcinoma (CCA) is a highly lethal subtype of hepatobiliary cancer that is often resistant to immune checkpoint inhibitor therapies. We evaluated the effects of IDH1 mutations in CCA cells on the tumor immune microenvironment and identified opportunities for therapeutic intervention.

Approach And Results: Analysis of 2606 human CCA tumors using deconvolution of RNA-sequencing data identified decreased CD8+ T cell and increased M2-like tumor-associated macrophage (TAM) infiltration in IDH1 -mutant compared to IDH1 wild-type tumors.

Effects of substance exposure on gametes and pre-implantation embryos: a narrative review.

Substance use refers to the consumption of drugs that have varying degrees of impact on a persons' physical, mental and emotional well-being. While the adverse health effects of drugs have been extensively documented, further research is needed to understand their impact on fertility. Studies have indicated that substance use affects both the male and female reproductive systems.

SpliceMutr Enables Pan-Cancer Analysis of Splicing-Derived Neoantigen Burden in Tumors.

SpliceMutr shows that splicing antigenicity changes in response to ICI therapies and that native modulation of the splicing machinery through mutations increases the contribution of splicing to the neoantigen load of some The Cancer Genome Atlas cancer subtypes. Future studies of the relationship between splicing antigenicity and immune checkpoint inhibitor response pan-cancer are essential to establish the interplay between antigen heterogeneity and immunotherapy regimen on patient response.