Targeting Axl favors an antitumorigenic microenvironment that enhances immunotherapy responses by decreasing Hif-1α levels

• DOI: 10.1073/pnas.2023868118
• Publication Date: 2021-07-15T19:40:13Z
• Authors: Marie-Anne Goyette; Islam E. Elkholi; Chloé Apcher; Hellen Kuasne; Carla V. Rothlin; William J. Muller; Darren E. Richard; Morag Park; Jean-Philippe Gra...; Jean-François Côté
• Keywords: Hypoxia; Proinflammatory cytokine

Significance A significant pool of HER2 + breast cancer patients are either unresponsive or become resistant to standards care. New therapeutic approaches exploiting the tumor microenvironment, including immunotherapies, attractive. Hypoxia shapes microenvironment toward therapy resistance and metastasis. Here, we report a role for AXL receptor tyrosine kinase in hypoxic response by promoting HIF-1α expression. Interfering with Axl preclinical model normalizes blood vessels promotes proinflammatory that enhances immunotherapy reduce primary metastatic burdens. Clinical trials so far suggest achieving responses cancers might be challenging, our data provide an important insight circumvent roadblock.