CD39+ tissue-resident memory CD8+ T cells with a clonal overlap across compartments mediate antitumor immunity in breast cancer

Yong Joon Lee, Jee Ye Kim, Seung Hyuck Jeon, Heejin Nam, Jae Hyung Jung, Minwoo Jeon, Eui Soon Kim, Soong June Bae, Juneyoung Ahn, Tae Kyung Yoo, Woo Young Sun, Sung Gwe Ahn, Joon Jeong, Su Hyung Park, Woo Chan Park, Seung Il Kim, Eui Cheol Shin

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)


Despite being a standard treatment option in breast cancer, immune checkpoint inhibitors (ICIs) are only efficacious for a subset of patients. To gain a better understanding of the antitumor immune response in breast cancer, we examined the heterogeneity of CD8+ T cells in tumors, metastatic lymph nodes (mLNs), and peripheral blood from patients with early breast cancer (n = 131). Among tissue-resident memory CD8+ T (TRM) cells, including virus- and tumor-specific CD8+ T cells, CD39 expression was observed in a tumor-specific and exhausted subpopulation in both tumors and mLNs. CD39+ TRM cells from tumors and mLNs exhibited a phenotypic similarity and clonally overlapped with each other. Moreover, tumor or mLN CD39+ TRM cells clonally overlapped with CD39- TRM and non-TRM cells in the same compartment, implying a tissue-specific differentiation process. These inter-subpopulationally overlapping CD39+ TRM clonotypes were frequently detected among effector memory CD8+ T cells in peripheral blood, suggesting a systemic clonal overlap. CD39+ TRM cell enrichment was heterogeneous among molecular subtypes of breast cancer, which is associated with the different role of antitumor immune responses in each subtype. In vitro blockade of PD-1 and/or CTLA-4 effectively restored proliferation of CD39+ TRM cells and enhanced cytokine production by CD8+ T cells from tumors or mLNs, particularly in the presence of CD39+ TRM enrichment. This suggests that CD39+ TRM cells have a capacity for functional restoration upon ICI treatment. Thus, our study indicates that CD39+ TRM cells with a clonal overlap across compartments are key players in antitumor immunity in breast cancer.

Original languageEnglish
Pages (from-to)eabn8390
JournalScience immunology
Issue number74
Publication statusPublished - 2022 Aug 26

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology


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