CD8+T cell activation in cancer comprises an initial activation phase in lymph nodes followed by effector differentiation within the tumor

Improvements in tumor immunotherapies depend on better understanding of the anti-tumor T cell response. By studying human tumor-draining lymph nodes (TDLNs), we found that activated CD8+ T cells in TDLNs shared functional, transcriptional, and epigenetic traits with TCF1+ stem-like cells in the tumor. The pheno-type and TCR overlap suggested that these TDLN cells were precursors to tumor-resident stem-like CD8+ T cells. Murine tumor models revealed that tumor-specific CD8+ T cells were activated in TDLNs but lacked an effector phenotype. These stem-like cells migrated into the tumor, where additional co-stimulation from antigen-presenting cells drove effector differentiation. This model of CD8+ T cell activation in response to cancer is different from that of canonical CD8+ T cell activation to acute viruses, and it proposes two stages of tumor-specific CD8+ T cell activation: initial activation in TDLNs and subsequent effector program acqui-sition within the tumor after additional co-stimulation.

Automated summary

Improvements in tumor immunotherapies rely on understanding the T cell response to tumors. By studying tumor-draining lymph nodes (TDLNs), it was discovered that activated CD8+ T cells in TDLNs shared characteristics with stem-like cells in tumors. These TDLN cells were revealed to be precursors of tumor-resident stem-like CD8+ T cells. Murine tumor models showed that tumor-specific CD8+ T cells were activated in TDLNs and later differentiated into effector cells in the tumor with co-stimulation.