Tanoue et al. showed that in nivolumab-treated patients with ESCC, intratumoral CD39+PD-1+ CD8+ T cells were heterogeneous, comprising a precursor stem-like exhausted TCF1+(CD39+ Tpex) subpopulation localized to the stroma and concentrated adjacent to tertiary lymphoid structures, which differentiated and migrated to localize within the tumor parenchyma as TCF-1−CD39+PD-1+ differentiated (more cytotoxic) Tex cells. ICB response was positively correlated with CD39+ Tpex cell abundance in tumors, but not with PD-L1 expression scores. Circulating proliferative CD39+ Tpex cell levels increased in responders following ICB therapy.
Contributed by Paula Hochman
ABSTRACT: Despite the success of immune checkpoint blockade (ICB) therapy for esophageal squamous cell cancer, the key immune cell populations that affect ICB efficacy remain unclear. Here, imaging mass cytometry of tumor tissues from ICB-treated patients identifies a distinct cell population of CD39(+)PD-1(+)CD8(+) T cells, specifically the TCF1(+) subset, precursor exhausted T (CD39(+) Tpex) cells, which positively correlate with ICB benefit. CD39(+) Tpex cells are predominantly in the stroma, while differentiated CD39(+) exhausted T cells are abundantly and proximally within the parenchyma. Notably, CD39(+) Tpex cells are concentrated within and around tertiary lymphoid structure (TLS). Accordingly, tumors harboring TLSs have more of these cells in tumor areas than tumors lacking TLSs, suggesting Tpex cell recruitment from TLSs to tumors. In addition, circulating CD39(+) Tpex cells are also increased in responders following ICB therapy. Our findings show that this unique subpopulation of CD39(+)PD-1(+)CD8(+) T cells is crucial for ICB benefit, and suggest a key role in TLS-mediated immune responses against tumors.
Author Info: (1) Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. (2) Department of Medicine and Biosystemic Science, Grad
Author Info: (1) Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. (2) Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Department of Oncology and Social Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. (3) Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. (4) Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. (5) Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. (6) Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. (7) Department of Hematology/Oncology, Japan Community Healthcare Organization Kyushu Hospital, Fukuoka, Japan. (8) Department of Imaging Science Program, McKelvey School of Engineering, Washington University in St. Louis, St. Louis, MO, USA. (9) Department of Medical Oncology, NHO National Hospital Organization Kyushu Medical Center, Fukuoka, Japan. (10) Department of Medical Oncology, Hamanomachi Hospital, Fukuoka, Japan. (11) Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Department of Oncology and Social Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. (12) Department of Medical Oncology, Kitakyushu Municipal Medical Center, Fukuoka, Japan. (13) Department of Medical Oncology, Fukuoka Wajiro Hospital, Fukuoka, Japan. (14) Department of Medical Oncology, St Mary's Hospital, Kurume, Japan. (15) Department of Medical Oncology, Hamanomachi Hospital, Fukuoka, Japan. (16) Department of Gastrointestinal and Medical Oncology, National Kyushu Cancer Center, Fukuoka, Japan. (17) Department of Medical Oncology, Sasebo Kyosai Hospital, Nagasaki, Japan. (18) Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. (19) Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. (20) Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Department of Pathology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan. (21) Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. (22) Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. (23) Department of Oncology and Social Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. baba.eishi.889@m.kyushu-u.ac.jp.
