Tumor aneuploidy correlates with markers of immune evasion and with reduced response to immunotherapy

TLDR

Chromosomal instability in tumors limits the effectiveness of cancer immunotherapy, which yields durable responses only in a subset of patients. The study aims to identify tumor features that correlate with immunotherapy response to develop predictive biomarkers and understand underlying mechanisms. Highly aneuploid tumors exhibit reduced expression of immune effector markers and are associated with poorer response to checkpoint blockade, indicating that aneuploidy promotes immune evasion. Published in Science (doi:10.1126/science.aaf8399) by Davoli et al.

Abstract

Chromosomal chaos and tumor immunity Cancer immunotherapy produces durable clinical responses in only a subset of patients. Identification of tumor characteristics that correlate with responses could lead to predictive biomarkers and shed light on causal mechanisms. Davoli et al. found that human tumors with extensive aneuploidy—i.e., that display a highly abnormal number of chromosomes and chromosomal segments—express fewer markers of the immune cells responsible for tumor destruction. In a retrospective analysis of clinical trial data, they found that melanoma patients with highly aneuploid tumors were less likely to benefit from immune checkpoint blockade therapy than patients whose tumors had a more normal karyotype. Thus, aneuploidy appears to enhance the ability of tumors to evade the immune system. Science , this issue p. 10.1126/science.aaf8399