The efficacy of immune checkpoint blockade (ICB) varies in different cancer patients, such as microsatellite instable (MSI) and stable (MSS) colorectal cancer (CRC) patients. To illustrate the underlying mechanisms, we utilized scRNA-seq to evaluate T cell subsets from CRC patients, identifying dynamic relationships of these T cells by a new analysis framework, STARTRAC. Importantly, we uncovered the intriguing association between CXCL13+ Th1-like cells and MSI CRC patients, providing a rationale for the high response rate to ICB in these patients. To further delineate the complex interactions in CRC, we performed combined single-cell analyses in CRC patients and murine tumor models under myeloid-targeted immunotherapies. Interestingly, anti-CD40 agonist treatment preferentially activated the Ccl22+ cDC1 population and increased Th1-like T cells. By contrast, anti-CSF1R blockade treatment spared pro-angiogenic SPP1+ TAMs, providing a previously unrecognized mechanism for tumor resistance to such treatment. Collectively, our studies provide new paradigms for dissecting the dynamic relationships and underlying mechanisms of therapeutic strategies in other diseases.
 

单细胞组学，肿瘤免疫，免疫治疗