Subcapsular sinus macrophages promote melanoma metastasis to the sentinel lymph nodes via an IL-1α-STAT3 axis
| Autor: | Tommaso Virgilio, Joy Bordini, Luciano Cascione, Giulio Sartori, Irene Latino, Daniel Molina Romero, Cristina Leoni, Murodzhon Akhmedov, Andrea Rinaldi, Alberto J. Arribas, Diego Morone, S. Morteza Seyed Jafari, Marina Bersudsky, Aner Ottolenghi, Ivo Kwee, Anna Maria Chiaravalli, Fausto Sessa, Robert E. Hunger, Antonino Bruno, Lorenzo Mortara, Elena Voronov, Silvia Monticelli, Ron N. Apte, Francesco Bertoni, Santiago F. Gonzalez |
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| Rok vydání: | 2022 |
| Předmět: |
Cancer Research
Skin Neoplasms Sentinel Lymph Node Biopsy Macrophages Immunology 610 Medicine & health Mice Melanoma. Subcapsular sinus macrophages. Sentinel lymph nodes. IL1a–STAT3 axis. Immunotherapy approach Lymphatic Metastasis Tumor Microenvironment Animals Lymph Nodes Sentinel Lymph Node Melanoma Lymphatic Vessels |
| Zdroj: | Virgilio, Tommaso; Bordini, Joy; Cascione, Luciano; Sartori, Giulio; Latino, Irene; Molina Romero, Daniel; Leoni, Cristina; Akhmedov, Murodzhon; Rinaldi, Andrea; Arribas, Alberto J; Morone, Diego; Seyed Jafari, S Morteza; Bersudsky, Marina; Ottolenghi, Aner; Kwee, Ivo; Chiaravalli, Anna Maria; Sessa, Fausto; Hunger, Robert E; Bruno, Antonino; Mortara, Lorenzo; ... (2022). Subcapsular sinus macrophages promote melanoma metastasis to the sentinel lymph nodes via an IL-1α-STAT3 axis. Cancer immunology research, 10(12), pp. 1525-1541. American Association for Cancer Research 10.1158/2326-6066.CIR-22-0225 |
| DOI: | 10.48350/173588 |
| Popis: | During melanoma metastasis, tumor cells originating in the skin migrate via lymphatic vessels to the sentinel lymph node (sLN). This process facilitates tumor cell spread across the body. Here, we characterized the innate inflammatory response to melanoma in the metastatic microenvironment of the sLN. We found that macrophages located in the subcapsular sinus (SS) produced protumoral IL1α after recognition of tumoral antigens. Moreover, we confirmed that the elimination of LN macrophages or the administration of an IL1α-specific blocking antibody reduced metastatic spread. To understand the mechanism of action of IL1α in the context of the sLN microenvironment, we applied single-cell RNA sequencing to microdissected metastases obtained from animals treated with the IL1α-specific blocking antibody. Among the different pathways affected, we identified STAT3 as one of the main targets of IL1α signaling in metastatic tumor cells. Moreover, we found that the antitumoral effect of the anti-IL1α was not mediated by lymphocytes because Il1r1 knockout mice did not show significant differences in metastasis growth. Finally, we found a synergistic antimetastatic effect of the combination of IL1α blockade and STAT3 inhibition with stattic, highlighting a new immunotherapy approach to preventing melanoma metastasis. |
| Databáze: | OpenAIRE |
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