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<p>Age-related increases in cancer have traditionally been attributed to compromised antitumor immunity of exhausted and dysfunctional CD8⁺ T cells. Here we provide an alternative mechanism: in aging, cancer also progresses with the help of fully functional CD8⁺ T cells. These transcriptionally and epigenetically distinct cells (termed double-positive CD8<sup>+</sup> T cells (DP8)) express CD39, CD73, CD101 and CXCR6 on their surface and accumulate during healthy aging in mice, requiring B cells presenting cognate antigens. In aged mice, progressing tumors recruit DP8 cells via the CXCL16–CXCR6 axis to suppress antitumor CD4<sup>+</sup> T cells in an ADP/adenosine-dependent manner, and targeting DP8 cell function or recruitment can reverse tumor growth in aged mice. This tumor-promoting mechanism of DP8 cells appears to be conserved in older humans, as we detected DP8-like cells in various tumors, including late-onset breast cancer. We propose that this tumor-promoting role of CD8<sup>+</sup> T cells should be considered in the development of therapeutics tailored for older humans.</p>

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A distinct population of CD8+ T cells expressing CD39 and CD73 accumulates with age and supports cancer progression

  • 期刊论文

  • 发表日期：

    2025年9月25日

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  • Monica Bodogai,
  • Bongsoo Park,
  • Fatima-Zohra Braikia,
  • Fnu Naqing,
  • Konda Kumaraswami,
  • Chen Chen,
  • Emeline Ragonnaud,
  • Sharon Stack,
  • Steffen Ormanns,
  • Michael Günther,
  • Hellen Ishikawa-Ankerhold,
  • Supriyo De,
  • Luigi Ferrucci,
  • Ranjan Sen,
  • Zhana Duren,
  • Isabel Beerman,
  • Arya Biragyn

摘要

Age-related increases in cancer have traditionally been attributed to compromised antitumor immunity of exhausted and dysfunctional CD8⁺ T cells. Here we provide an alternative mechanism: in aging, cancer also progresses with the help of fully functional CD8⁺ T cells. These transcriptionally and epigenetically distinct cells (termed double-positive CD8+ T cells (DP8)) express CD39, CD73, CD101 and CXCR6 on their surface and accumulate during healthy aging in mice, requiring B cells presenting cognate antigens. In aged mice, progressing tumors recruit DP8 cells via the CXCL16–CXCR6 axis to suppress antitumor CD4+ T cells in an ADP/adenosine-dependent manner, and targeting DP8 cell function or recruitment can reverse tumor growth in aged mice. This tumor-promoting mechanism of DP8 cells appears to be conserved in older humans, as we detected DP8-like cells in various tumors, including late-onset breast cancer. We propose that this tumor-promoting role of CD8+ T cells should be considered in the development of therapeutics tailored for older humans.