Nerve- and Airway-Associated Interstitial Macrophages Regulate Anti-Tumor CD8 T Cell Immunity in Tumors in the Lung

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Presentation Time: 02:45 PM - 03:00 PM
Abstract ID: 6121 - B

Presenting Author:
Eric Bartnicki , PhD Candidate at NYU Grossman Sch. of Med.

Abstract:

The suboptimal response rates among cancer patients receiving T cell-based immunotherapy underscore the necessity of addressing additional facets of the immune system that may contribute to tumor promotion. Macrophages are a main immune cell subset in tumors and elucidating their immunomodulatory roles on T cell-mediated anti-tumor responses is paramount. We previously identified a novel macrophage subset known as Nerve- and Airway-associated interstitial Macrophages (NAMs), which exhibit a remarkable immunoregulatory phenotype. Thus, we investigated the hypothesis that NAMs promote tumor growth and metastasis. Using the B16F10 melanoma-based lung metastatic model, we observed that unlike alveolar macrophages (AMs), NAMs uniquely localize to tumors that form along large airways and vasculature. Moreover, tumors that were primarily infiltrated by NAMs exhibited less CD8 T cell presence when compared to tumors devoid of NAMs, suggesting that NAMs regulate anti-tumor T cell responses. Exclusive depletion of NAMs resulted in strikingly lower tumor burden in the lungs, which was associated with a significant increase in CD8 T cell recruitment to the TME; and increased presence of anti-tumor ‘CD8-DC-CD4 triad’ interactions within the TME with CD8 T cells exhibiting an exhausted progenitor-like anti-tumor phenotype. Our findings also furnish compelling evidence to redirect our endeavors towards prioritizing NAMs as a therapeutic target in lung tumors.