Stem-like CD8 T cells mediate response of adoptive cell immunotherapy against human cancer

Science. 2020 Dec 11;370(6522):1328-1334. doi: 10.1126/science.abb9847.


Adoptive T cell therapy (ACT) using ex vivo-expanded autologous tumor-infiltrating lymphocytes (TILs) can mediate complete regression of certain human cancers. The impact of TIL phenotypes on clinical success of TIL-ACT is currently unclear. Using high-dimensional analysis of human ACT products, we identified a memory-progenitor CD39-negative stem-like phenotype (CD39-CD69-) associated with complete cancer regression and TIL persistence and a terminally differentiated CD39-positive state (CD39+CD69+) associated with poor TIL persistence. Most antitumor neoantigen-reactive TILs were found in the differentiated CD39+ state. However, ACT responders retained a pool of CD39- stem-like neoantigen-specific TILs that was lacking in ACT nonresponders. Tumor-reactive stem-like TILs were capable of self-renewal, expansion, persistence, and superior antitumor response in vivo. These data suggest that TIL subsets mediating ACT response are distinct from TIL subsets enriched for antitumor reactivity.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Antigens, CD / analysis
  • Antigens, Differentiation, T-Lymphocyte / analysis
  • Apyrase / analysis
  • CD8-Positive T-Lymphocytes / chemistry
  • CD8-Positive T-Lymphocytes / immunology*
  • Female
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Lectins, C-Type / analysis
  • Lymphocytes, Tumor-Infiltrating / transplantation*
  • Melanoma / immunology
  • Melanoma / therapy*
  • Mice
  • Mice, Mutant Strains
  • Skin Neoplasms / immunology
  • Skin Neoplasms / therapy*


  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD69 antigen
  • Lectins, C-Type
  • Apyrase
  • ENTPD1 protein, human