意大利都灵大学Alberto Bardelli等研究人员合作发现，DNA错配修复异质性肿瘤的遗传和药理调控促进免疫监控。该研究于2022年12月29日在线发表于国际一流学术期刊《癌细胞》。

Title: Genetic and pharmacological modulation of DNA mismatch repair heterogeneous tumors promotes immune surveillance

Author: Vito Amodio, Simona Lamba, Rosaria Chilà, Chiara M. Cattaneo, Benedetta Mussolin, Giorgio Corti, Giuseppe Rospo, Enrico Berrino, Claudio Tripodo, Federica Pisati, Alice Bartolini, Maria Costanza Aquilano, Silvia Marsoni, Gianluca Mauri, Caterina Marchiò, Sergio Abrignani, Federica Di Nicolantonio, Giovanni Germano, Alberto Bardelli

Issue&Volume: 2022-12-29

Abstract: Patients affected by colorectal cancer (CRC) with DNA mismatch repair deficiency (MMRd), often respond to immune checkpoint blockade therapies, while those with mismatch repair-proficient (MMRp) tumors generally do not. Interestingly, a subset of MMRp CRCs contains variable fractions of MMRd cells, but it is unknown how their presence impacts immune surveillance. We asked whether modulation of the MMRd fraction in MMR heterogeneous tumors acts as an endogenous cancer vaccine by promoting immune surveillance. To test this hypothesis, we use isogenic MMRp (Mlh1+/+) and MMRd (Mlh1/) mouse CRC cells. MMRp/MMRd cells mixed at different ratios are injected in immunocompetent mice and tumor rejection is observed when at least 50% of cells are MMRd. To enrich the MMRd fraction, MMRp/MMRd tumors are treated with 6-thioguanine, which leads to tumor rejection. These results suggest that genetic and pharmacological modulation of the DNA mismatch repair machinery potentiate the immunogenicity of MMR heterogeneous tumors.

DOI: 10.1016/j.ccell.2022.12.003

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(22)00589-X