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The ASB2α protein is a key regulator of the immune response in colorectal cancer

More knowledge of the mechanisms controlling T lymphocyte functions is a major challenge for therapeutic manipulations of immune responses. Although treating cancer through the adoptive transfer of T cells has long relied on cytotoxic T cells, several data including preclinical data, have emphasized the potential of CD4 effector T cells to mediate tumor rejection. This work reveals an unsuspected regulatory pathway controlling the immune response in colorectal cancer. This study is published in Cancer Immunology Research, the journal of the American Association for Cancer Research, on June 7, 2019.

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It is now well-established that the immune system plays major roles in the development, evolution, response to treatment and outcome of cancers. Notably, the quality of the immune response is an important prognostic factor for cancer patients and this is particularly true for patients with colorectal cancer, one of the most common malignant neoplasms with poor response to treatment and high mortality. Therefore, deciphering the mechanisms linking immune response and colorectal cancer may facilitate the development of new therapeutic approaches.
Few years ago, researchers of P. Lutz lab identified the ASB2α E3 ubiquitin ligase that is involved in the selective degradation of protein targets and provided evidences that it plays important roles in major biological functions in both physiological and pathological settings. The researchers have now showed that ASB2α controls the effector functions of Th2 cells and exerts pro-tumoral effects in colorectal cancer. Moreover, reduced ASB2α expression resulted in diminished Th2 cell function and subsequently in enhanced type 1 anti-tumor immune response.
These new results now substantiate a pro-tumor activity of Th2 cells in colorectal cancer. They suggest that ASB2α may serve as a therapeutic target in colorectal cancer and more broadly for other pathologies driven by Th2 immune responses.
This research was supported by the Centre National de la Recherche Scientifique, the University of Toulouse, the ITMO Cancer Aviesan (Alliance Nationale Pour les Sciences de la Vie et de la Santé, National Alliance for Life Science and Health - Cancer Plan), by grants from the Comité Midi-Pyrénées de la Ligue contre le Cancer and from the Fondation ARC pour la recherche sur le cancer, and by fellowships of the French Ministry of Higher Education and Research, of the Société Française d’Hématologie and of Fonroga (Fondation Roland Garrigou pour la Culture et la Santé).

figure_lutz.jpg Legend: Tumor (T) in the mouse colon

© Camille Spinner, Arnaud Métais & Pierre Lutz

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Reference:

The E3 ubiquitin ligase Asb2α in T helper 2 cells negatively regulates anti-tumor immunity in colorectal cancer., Spinner CA, Lamsoul I, Métais A, Febrissy C, Moog-Lutz C and Lutz PG. Cancer Immunology Research. June 7, 2019