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In vivo armed macrophages curb liver metastasis through tumor-reactive T-cell rejuvenation
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In vivo armed macrophages curb liver metastasis through tumor-reactive T-cell rejuvenation
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Journal Article
In vivo armed macrophages curb liver metastasis through tumor-reactive T-cell rejuvenation
2025
Overview
Despite recent progress in cancer treatment, liver metastases persist as an unmet clinical need. Here, we show that arming liver and tumor-associated macrophages in vivo to co-express tumor antigens (TAs), IFNα, and IL-12 unleashes robust anti-tumor immune responses, leading to the regression of liver metastases. Mechanistically, in vivo armed macrophages expand tumor reactive CD8
+
T cells, which acquire features of progenitor exhausted T cells and kill cancer cells independently of CD4
+
T cell help. IFNα and IL-12 produced by armed macrophages reprogram antigen presenting cells and rewire cellular interactions, rescuing tumor reactive T cell functions. In vivo armed macrophages trigger anti-tumor immunity in distinct liver metastasis mouse models of colorectal cancer and melanoma, expressing either surrogate tumor antigens, naturally occurring neoantigens or tumor-associated antigens. Altogether, our findings support the translational potential of in vivo armed liver macrophages to expand and rejuvenate tumor reactive T cells for the treatment of liver metastases.
Liver metastases are a clinical problem, with low responses to immunotherapy. Here, authors coordinate expression of tumor antigens IFNα and IL-12 in liver and tumor associated macrophages to rejuvenate tumor reactive T cells and eliminate liver metastases.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/51
/ 38/91
/ 42
/ 42/41
/ 42/44
/ 49
/ 59/57
/ Animals
/ Antigens
/ Antigens, Neoplasm - immunology
/ Antigens, Neoplasm - metabolism
/ Cancer
/ CD4-Positive T-Lymphocytes - immunology
/ CD8-Positive T-Lymphocytes - immunology
/ Colorectal Neoplasms - immunology
/ Colorectal Neoplasms - pathology
/ Female
/ Humanities and Social Sciences
/ Humans
/ Interferon-alpha - immunology
/ Interferon-alpha - metabolism
/ Liver
/ Liver Neoplasms - immunology
/ Melanoma
/ Mice
/ Science
/ Tumor-Associated Macrophages - immunology
/ Tumors
