【解放日报】免疫治疗耐药？中国科学家发现显著提升T细胞“战斗力”靶点

Core Insights - T cells, akin to special forces in the human body, are crucial for combating foreign invaders, yet their effectiveness against certain tumors has been historically questioned since 1968 due to the tumor microenvironment's role in immune therapy resistance [1][2] - Recent research has identified how tumors modify their microenvironment through genetic mutations, creating an immune "barrier" that limits the efficacy of immunotherapy [1][3] Group 1: Tumor Microenvironment and Immune Response - Tumor metastasis is the leading cause of cancer-related deaths, with the microenvironment formed during this process acting as an "ecosystem" for tumor survival [2] - The research team categorized 391 common tumor suppressor gene-driven metastatic microenvironments into seven types, revealing varied responses to immunotherapy based on the microenvironment [2] - In microenvironments unresponsive to immunotherapy, collagen deposition was significantly increased, creating a protective "web" that hinders T cell effectiveness [2] Group 2: Strategies to Overcome Resistance - A key molecule, lysyl oxidase-like protein 2, was identified as a target; inhibiting it significantly reduced collagen deposition, allowing T cells to penetrate the tumor and enhance immunotherapy effectiveness [3] - The team utilized AI algorithms to identify causal genes related to the immune status of the tumor microenvironment, developing a model that accurately predicts immunotherapy outcomes based on 30 feature genes [3] - This research provides a technological platform for addressing immunotherapy resistance in metastatic tumors, with newly discovered molecules offering potential strategies for overcoming this challenge [3]