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ASB2α in immune response in cancer

 

The immune system plays major roles in cancer development and response to treatment. Data have emphasized the potential of CD4 positive T cells to mediate tumor rejection. CD4 positive T cells mature into distinct subtypes with diverse functions. Among them, T helper 2 (Th2) cells represent a major component in the regulation of humoral immunity and allergic inflammatory responses, but their roles in tumor immunity remain under investigated. In our Cancer Immunology Research article (Spinner et al., 2019), we questioned whether ASB2α has a role in Th2 cells and in the immune response to colorectal cancer (CRC). A Th1-dominated immune response is known to be associated with a positive outcome in CRC. We found that high levels of ASB2 in CRC biopsies correlated with reduced relapse-free survival time. To elucidate a potential functional relationship between ASB2 and CRC, we investigated the impact of ASB2 loss on tumor development using a mouse model of CRC. We observed a diminished Th2 function that correlated with increased IFN-γ production and an enhanced type 1 anti-tumor immune response in ASB2-deficient mice. Our work suggests that ASB2α promotes a Th2 phenotype in vivo, which in turn is associated with tumor progression in a mouse model of colitis. Since E3 ubiquitin ligases are druggable, ASB2α might be a promising pharmacological target to modulate Th2 response in cancer.

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