IL-9 immunotherapy for lung tumor growth

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Presentation Time: 03:00 PM - 03:15 PM
Abstract ID: 5750 - B

Presenting Author:
Jilu Zhang , Assistant Research Professor at Indiana Univ. Sch. of Med., Indiana Univ. Simon Comp. Cancer Ctr.

Abstract:

Interleukin 9 (IL-9) is produced by T cells, mast cells, and innate lymphoid cells, and has pleiotropic activities in enhancing immune cell recruitment and function. In contrast to the anti-tumoral property of IL-9 in various cancers, we and others have reported endogenous IL-9 signaling promotes tumor growth in the lung. The therapeutic potential of IL-9 blockade is not well studied. In the present study, we evaluate the therapeutic efficacy of IL-9 blockade by IL-9-neutralizing antibodies in a melanoma lung metastasis model and a carcinogen-induced spontaneous lung cancer model by defining tumor burden and cellular components in lung tissue. Mice receiving anti-IL-9 treatment exhibit a significantly lower number of lung tumor foci compared to control IgG-treated mice. Cellular analysis indicates that IL-9 blockade inhibits the expansion of immunosuppressive lung interstitial macrophages and decreases arginase-1 production from lung myeloid cells. Consequently, arginase activity in the lung is inhibited, leading to elevated levels of free L-Arginine. Moreover, IL-9 blockade reduces a population of activated regulatory T cells while promoting an effector memory phenotype in conventional T cells. In conclusion, anti-IL-9 treatment effectively reduces the lung tumor burden by altering the immunosuppressive tumor microenvironment in both models. Thus, IL-9 blockade may be a potential immunotherapeutic strategy for inhibiting tumor growth in the lung.