A type 2 immune response may help in the treatment of cancer, according to two groundbreaking new studies.
The type 2 response is triggered by parasitic infections, such as worms and, according to the European researchers, has not previously been regarded as acting against cancer.
The initial idea arose from analysis of cells from the first patients to receive CAR-T therapy as treatment for acute lymphoblastic leukaemia. Researchers analysed nearly 700,000 CAR-T cells from 82 patients. Writing in Nature, they report that this showed that cells contained unusual amounts of IL4, a cytokine linked to the type 2 immune response.
A second study, reported simultaneously in Nature, involved an investigation on laboratory mice of the potential of type 2 immunotherapy. This included a modified, long-lasting version of IL-4, called Fc-IL-4. This was compared with standard immunotherapies alone.
The study showed that adding Fc-IL-4 to immunotherapies led to improved survival in mice, even when they had received additional cancer cells. Detailed analysis suggested that IL-4 was promoting glycolysis, perhaps revitalising “exhausted” T cells.
Researcher Professor Li Tang, of the Ecole Polytechnique Fédérale de Lausanne, Switzerland, said: “Our study not only sheds light on the synergy between these two types of immune response, but also unveils an innovative strategy for advancing next-generation cancer immunotherapy by integrating type 2 immune factors.
“Overall, I hope that these two studies – one preclinical mechanistic and one clinical – will inspire the field to challenge the type 1-centric paradigm in cancer immunotherapy and re-examine the role of type 2 immunity.”
Source:
Bai Z, Feng B, McClory SE, de Oliveira BC, Diorio C, Gregoire C, Tao B, Yang L, Zhao Z, Peng L, Sferruzza G, Zhou L, Zhou X, Kerr J, Baysoy A, Su G, Yang M, Camara PG, Chen S, Tang L, June CH, Melenhorst JJ, Grupp SA, Fan R. (2024) “Single-cell CAR T atlas reveals type 2 function in 8-year leukaemia remission.” Nature, 25 September 2024, doi: 10.1038/s41586-024-07762-w
Link: https://www.nature.com/articles/s41586-024-07762-w
Feng B, Bai Z, Zhou X, Zhao Y, Xie YQ, Huang X, Liu Y, Enbar T, Li R, Wang Y, Gao M, Bonati L, Peng MW, Li W, Tao B, Charmoy M, Held W, Melenhorst JJ, Fan R, Guo Y, Tang L. (2024) “The type 2 cytokine Fc–IL-4 revitalizes exhausted CD8+ T cells against cancer.” Nature, 25 September 2024, doi:
Link: https://www.nature.com/articles/s41586-024-07962-4
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