Intratumoral immune triads are required for immunotherapy-mediated elimination of solid tumors Journal Article

   


Authors: Espinosa-Carrasco, G.; Chiu, E.; Scrivo, A.; Zumbo, P.; Dave, A.; Betel, D.; Kang, S. W.; Jang, H. J.; Hellmann, M. D.; Burt, B. M.; Lee, H. S.; Schietinger, A.
Article Title: Intratumoral immune triads are required for immunotherapy-mediated elimination of solid tumors
Abstract: Tumor-specific CD8+ T cells are frequently dysfunctional and unable to halt tumor growth. We investigated whether tumor-specific CD4+ T cells can be enlisted to overcome CD8+ T cell dysfunction within tumors. We find that the spatial positioning and interactions of CD8+ and CD4+ T cells, but not their numbers, dictate anti-tumor responses in the context of adoptive T cell therapy as well as immune checkpoint blockade (ICB): CD4+ T cells must engage with CD8+ T cells on the same dendritic cell during the effector phase, forming a three-cell-type cluster (triad) to license CD8+ T cell cytotoxicity and cancer cell elimination. When intratumoral triad formation is disrupted, tumors progress despite equal numbers of tumor-specific CD8+ and CD4+ T cells. In patients with pleural mesothelioma treated with ICB, triads are associated with clinical responses. Thus, CD4+ T cells and triads are required for CD8+ T cell cytotoxicity during the effector phase and tumor elimination. © 2024
Keywords: controlled study; unclassified drug; nonhuman; neoplasm; neoplasms; cd8 antigen; cd8+ t lymphocyte; cd8-positive t-lymphocytes; mouse; animal; animals; mice; animal tissue; cancer immunotherapy; confocal microscopy; dendritic cell; animal experiment; animal model; cell line, tumor; tumor antigen; mice, inbred c57bl; c57bl mouse; immunology; dendritic cells; immunotherapy; epigenetics; cd4+ t lymphocyte; cd4-positive t-lymphocytes; cytotoxic t lymphocyte; tumor cell line; pleura mesothelioma; tumor; therapy; adoptive immunotherapy; immunotherapy, adoptive; cd4 t cell; cd8 t cell; lymphoid enhancer factor 1; programmed death 1 receptor; tumor microenvironment; early growth response factor 2; lymphocyte activation gene 3 protein; interleukin 7 receptor; procedures; glycoprotein p 15095; immune checkpoint blockade; immune checkpoint inhibitor; triad; cancer; humans; human; male; female; article; immune checkpoint inhibitors; solid malignant neoplasm; hepatitis a virus cellular receptor 2; cd39 antigen; adoptive t cell transfer; cd244 antigen; cytochrome p450 2b4
Journal Title: Cancer Cell
Volume: 42
Issue: 7
ISSN: 1535-6108
Publisher: Cell Press  
Date Published: 2024-07-08
Start Page: 1202
End Page: 1216.e8
Language: English
DOI: 10.1016/j.ccell.2024.05.025
PUBMED: 38906155
PROVIDER: scopus
PMCID: PMC11413804
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85197028914&doi=10.1016%2fj.ccell.2024.05.025&partnerID=40&md5=17fc79d7d2fb92d3416b3c443f1f7b0a
Notes: The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF. Corresponding MSK author is Andrea Schietinger -- Source: Scopus
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MSK Authors
  1. Matthew David Hellmann
    411 Hellmann
  2. Andrea Schietinger
    42 Schietinger
  3. Gabriel Espinosa Carrasco
    4 Espinosa Carrasco
  4. Asim Dave
    7 Dave
  5. Edison Yuhsiang Chiu
    1 Chiu
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