CD8<sup>+</sup> 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<sup>+</sup> T cells in TDLNs shared functional, transcriptional, and epigenetic traits with TCF1<sup>+</sup> stem-like cells in the tumor. The phenotype and TCR overlap suggested that these TDLN cells were precursors to tumor-resident stem-like CD8<sup>+</sup> T cells. Murine tumor models revealed that tumor-specific CD8<sup>+</sup> 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<sup>+</sup> T cell activation in response to cancer is different from that of canonical CD8<sup>+</sup> T cell activation to acute viruses, and it proposes two stages of tumor-specific CD8<sup>+</sup> T cell activation: initial activation in TDLNs and subsequent effector program acquisition within the tumor after additional co-stimulation.

  • Alemozaffar M
  • Barwick BG
  • Bilen MA
  • Cardenas MA
  • Cimmino C
  • Greenwald R
  • Gregorova P
  • Jansen C
  • Joshi S
  • Kissick H
  • Larsen C
  • Master V
  • Prokhnevska N
  • Reyes Moon A
  • Sanda M
  • Sobierajska E
  • Valanparambil RM
  • delBalzo L
PubMed ID
Appears In
Immunity, 2023, 56 (1)