Open AccessRegulatory T cell control of systemic immunity and immunotherapy response in liver metastasis
Author(s) -
James C. Lee,
Sadaf Mehdizadeh,
Jennifer A. Smith,
Arabella Young,
Ilgiz A. Mufazalov,
Cody T. Mowery,
Adil Daud,
Jeffrey A. Bluestone
Publication year - 2020
Publication title -
science immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.83
H-Index - 51
ISSN - 2470-9468
DOI - 10.1126/sciimmunol.aba0759
Subject(s) - immunotherapy , metastasis , immunity , immunology , cancer research , immune system , medicine , biology , cancer
Patients with cancer with liver metastasis demonstrate significantly worse outcomes than those without liver metastasis when treated with anti-PD-1 immunotherapy. The mechanism of liver metastases-induced reduction in systemic antitumor immunity is unclear. Using a dual-tumor immunocompetent mouse model, we found that the immune response to tumor antigen presence within the liver led to the systemic suppression of antitumor immunity. The immune suppression was antigen specific and associated with the coordinated activation of regulatory T cells (T regs ) and modulation of intratumoral CD11b + monocytes. The dysfunctional immune state could not be reversed by anti-PD-1 monotherapy unless T reg cells were depleted (anti-CTLA-4) or destabilized (EZH2 inhibitor). Thus, this study provides a mechanistic understanding and rationale for adding T reg and CD11b + monocyte targeting agents in combination with anti-PD-1 to treat patients with cancer with liver metastasis.