CD8+MT+ effector T cells from enlarged tumor-draining lymph nodes enhanced anti-tumor immunity and improved prognosis in colorectal cancer

Despite the critical role of tumor-draining lymph nodes (TDLNs) in immunity, their heterogeneity is poorly understood. We employ single-cell and bulk RNA sequencing (RNA-seq) to dissect the immune landscape of TDLNs in colorectal cancer (CRC) cohorts. We reveal that enlarged TDLNs (L-TDLNs) are enriched with CD8 + effector T (Teff) cells exhibiting a distinct metallothionein (MT)-positive signature. CD8 + MT + Teff cells exhibit heightened cytotoxicity and a stress-adapted phenotype, which are critical mediators of anti-tumor immunity. CD8 + MT + Teff cells originate from L-TDLNs, where they undergo specific differentiation, and subsequently migrate to tumor. Moreover, patients with a high level of CD8 + MT + Teff cells in tumor show a significant survival advantage, in particular those treated with adjuvant chemotherapy. These findings highlight the importance of L-TDLNs in shaping effective anti-tumor immune responses, proposing the CD8 + MT + Teff cells as a prognostic biomarker and potential therapeutic target in CRC.