Open AccessJAML promotes CD8 and γδ T cell antitumor immunity and is a novel target for cancer immunotherapy
Author(s) -
Joseph M. McGraw,
Flavian Thelen,
Eric Hampton,
Nelson E. Bruno,
Travis S. Young,
Wendy L. Havran,
Deborah A. Witherden
Publication year - 2021
Publication title -
the journal of experimental medicine/the journal of experimental medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.483
H-Index - 448
eISSN - 1540-9538
pISSN - 0022-1007
DOI - 10.1084/jem.20202644
Subject(s) - immunotherapy , cd8 , cancer research , tumor infiltrating lymphocytes , cancer immunotherapy , blockade , cytotoxic t cell , immunity , immunology , immune checkpoint , biology , immune system , t cell , receptor , in vitro , biochemistry
T cells are critical mediators of antitumor immunity and a major target for cancer immunotherapy. Antibody blockade of inhibitory receptors such as PD-1 can partially restore the activity of tumor-infiltrating lymphocytes (TILs). However, the activation signals required to promote TIL responses are less well characterized. Here we show that the antitumor activity of CD8 and γδ TIL is supported by interactions between junctional adhesion molecule–like protein (JAML) on T cells and its ligand coxsackie and adenovirus receptor (CXADR) within tumor tissue. Loss of JAML through knockout in mice resulted in accelerated tumor growth that was associated with an impaired γδ TIL response and increased CD8 TIL dysfunction. In mouse tumor models, therapeutic treatment with an agonistic anti-JAML antibody inhibited tumor growth, improved γδ TIL activation, decreased markers of CD8 TIL dysfunction, and significantly improved response to anti–PD-1 checkpoint blockade. Thus, JAML represents a novel therapeutic target to enhance both CD8 and γδ TIL immunity.