임세진 (성균관대 의과대학, Emory University School of Medicine) | 한빛사논문 > 한빛사

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성균관대 의과대학, Emory University School of Medicine

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Proc. Natl. Acad. Sci. USA, Oct 10 2023, 120 (41) | https://doi.org/10.1073/pnas.2221985120 Characteristics and anatomic location of PD-1+TCF1+ stem-like CD8 T cells in chronic viral infection and cancer.

Se Jin Im ^{# 1 2 3 *}, Rebecca C Obeng ^{# 1 2 4 5}, Tahseen H Nasti ^{1 2}, Daniel McManus ^{1 2}, Alice O Kamphorst ^{6 7}, Sivaram Gunisetty ^{1 2}, Nataliya Prokhnevska ^{1 8}, Jennifer W Carlisle ^{9 10}, Ke Yu ⁴, Gabriel L Sica ^{4 10 11}, Lucas E Cardozo ¹², André N A Gonçalves ¹², Haydn T Kissick ^{1 8}, Helder I Nakaya ¹², Suresh S Ramalingam ^{9 10 *}, Rafi Ahmed ^{1 2 *}

¹Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322.
²Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322.
³Department of Immunology, Sungkyunkwan University School of Medicine, Suwon 16419, Republic of Korea.
⁴Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322.
⁵Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106.
⁶Department of Immunology and Immunotherapy, Lipschultz Precision Immunology Institute, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029.
⁷Department of Oncological Sciences, Lipschultz Precision Immunology Institute, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029.
⁸Department of Urology, Emory University School of Medicine, Atlanta, GA 30322.
⁹Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA 30322.
¹⁰Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322.
¹¹Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213.
¹²Hospital Israelita Albert Eisnstein, Sao Paulo 05652, Brazil.

^#Contributed equally.
^*Corresponding author: correspondence to Se Jin Im, Suresh S Ramalingam or Rafi Ahmed

Abstract

CD8 T cells play an essential role in antitumor immunity and chronic viral infections. Recent findings have delineated the differentiation pathway of CD8 T cells in accordance with the progenitor-progeny relationship of TCF1⁺ stem-like and Tim-3 ⁺TCF1^- more differentiated T cells. Here, we investigated the characteristics of stem-like and differentiated CD8 T cells isolated from several murine tumor models and human lung cancer samples in terms of phenotypic and transcriptional features as well as their location compared to virus-specific CD8 T cells in the chronically lymphocytic choriomeningitis virus (LCMV)-infected mice. We found that CD8 tumor-infiltrating lymphocytes (TILs) in both murine and human tumors exhibited overall similar phenotypic and transcriptional characteristics compared to corresponding subsets in the spleen of chronically infected mice. Moreover, stem-like CD8 TILs exclusively responded and produced effector-like progeny CD8 T cells in vivo after antigenic restimulation, confirming their lineage relationship and the proliferative potential of stem-like CD8 TILs. Most importantly, similar to the preferential localization of PD-1⁺ stem-like CD8 T cells in T cell zones of the spleen during chronic LCMV infection, we found that the PD-1⁺ stem-like CD8 TILs in lung cancer samples are preferentially located not in the tumor parenchyma but in tertiary lymphoid structures (TLSs). The stem-like CD8 T cells are present in TLSs located within and at the periphery of the tumor, as well as in TLSs closely adjacent to the tumor parenchyma. These findings suggest that TLSs provide a protective niche to support the quiescence and maintenance of stem-like CD8 T cells in the tumor.

논문정보

형식Research article
게재일2023년 10월 (BRIC 등록일 2023-10-04)
연구진국내(교신)+국외 연구진
분야 생명과학 > 면역학

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