To explore IL9’s antitumor efficacy, Do-Thi, Park, and Park et al. determined that IL9 directly stimulated macrophage proliferation and polarized them towards an IFNγ-dependent proinflammatory M1 phenotype. Mechanistically, IL9 treatment re-educated TAMs and M2 macrophages towards the M1 phenotype, which resulted in T cell, DC, and NK cell recruitment into the TME via the release of CCL3/4 and CXCL9/10 chemokines. When TAMs and either B16F10 melanoma or 4T1 breast cancer cells were co-implanted into syngeneic mice, intraperitoneal IL9 treatment delayed tumor growth, suggesting that TAM reprogramming to facilitate immune cell influx could be a promising solid tumor therapy.
Contributed by Katherine Turner
ABSTRACT: Tumor-associated macrophages (TAM) are involved in tumor progression, metastasis, and immunosuppression. Because TAMs are highly plastic and could alter their phenotypes to proinflammatory M1 in response to environmental stimuli, reeducating TAMs has emerged as a promising approach to overcoming the challenges of solid cancer treatment. This study investigated the effect of IL9 on macrophage M1 polarization and verified its antitumor potential to retrain TAMs and promote chemokine secretion. We demonstrated that IL9 stimulated macrophage proliferation and polarized them toward the proinflammatory M1 phenotype in an IFNγ-dependent manner. Tumor-localized IL9 also polarized TAMs toward M1 in vivo and made them release CCL3/4 and CXCL9/10 to recruit antitumor immune cells, including T and natural killer cells, into the tumor microenvironment. Furthermore, peritoneal treatment with recombinant IL9 delayed the growth of macrophage-enriched B16F10 melanoma and 4T1 breast cancer in syngeneic mice, although IL9 treatment did not reduce tumor growth in the absence of macrophage enrichment. These results demonstrate the efficacy of IL9 in macrophage polarization to trigger antitumor immunity.
Author Info: (1) Institute of Membrane Proteins, POSTECH, Pohang, Republic of South Korea. (2) Department of Life Sciences, POSTECH, Pohang, Republic of South Korea. (3) Department of Life Scie
Author Info: (1) Institute of Membrane Proteins, POSTECH, Pohang, Republic of South Korea. (2) Department of Life Sciences, POSTECH, Pohang, Republic of South Korea. (3) Department of Life Sciences, POSTECH, Pohang, Republic of South Korea. (4) Institute of Membrane Proteins, POSTECH, Pohang, Republic of South Korea. (5) Institute of Membrane Proteins, POSTECH, Pohang, Republic of South Korea. (6) Gyeongbuk Institute for Bio Industry, Andong-si, Gyeongbuk, Republic of South Korea. (7) Department of Biochemistry, College of Natural Science, Chungnam National University, Daejeon, Republic of South Korea. (8) Institute of Biotechnology, Chungnam National University, Daejeon, Republic of South Korea. (9) Institute of Membrane Proteins, POSTECH, Pohang, Republic of South Korea. Department of Life Sciences, POSTECH, Pohang, Republic of South Korea.
