小柯机器人

美国纪念斯隆-凯特琳癌症中心Vinod P. Balachandran等研究人员合作发现，新抗原质量可预测胰腺癌幸存者的免疫编辑。相关论文于2022年5月19日在线发表在《自然》杂志上。

Author: uksza, Marta, Sethna, Zachary M., Rojas, Luis A., Lihm, Jayon, Bravi, Barbara, Elhanati, Yuval, Soares, Kevin, Amisaki, Masataka, Dobrin, Anton, Hoyos, David, Guasp, Pablo, Zebboudj, Abderezak, Yu, Rebecca, Chandra, Adrienne Kaya, Waters, Theresa, Odgerel, Zagaa, Leung, Joanne, Kappagantula, Rajya, Makohon-Moore, Alvin, Johns, Amber, Gill, Anthony, Gigoux, Mathieu, Wolchok, Jedd, Merghoub, Taha, Sadelain, Michel, Patterson, Erin, Monasson, Remi, Mora, Thierry, Walczak, Aleksandra M., Cocco, Simona, Iacobuzio-Donahue, Christine, Greenbaum, Benjamin D., Balachandran, Vinod P.

Issue&Volume: 2022-05-19

Abstract: Cancer immunoediting1 is a hallmark of cancer2 that predicts that lymphocytes kill more immunogenic cancer cells to cause less immunogenic clones to dominate a population. Although proven in mice1,3, whether immunoediting occurs naturally in human cancers remains unclear. Here, to address this, we investigate how 70 human pancreatic cancers evolved over 10 years. We find that, despite having more time to accumulate mutations, rare long-term survivors of pancreatic cancer who have stronger T cell activity in primary tumours develop genetically less heterogeneous recurrent tumours with fewer immunogenic mutations (neoantigens). To quantify whether immunoediting underlies these observations, we infer that a neoantigen is immunogenic (high-quality) by two features—‘non-selfness’  based on neoantigen similarity to known antigens4,5, and ‘selfness’  based on the antigenic distance required for a neoantigen to differentially bind to the MHC or activate a T cell compared with its wild-type peptide. Using these features, we estimate cancer clone fitness as the aggregate cost of T cells recognizing high-quality neoantigens offset by gains from oncogenic mutations. With this model, we predict the clonal evolution of tumours to reveal that long-term survivors of pancreatic cancer develop recurrent tumours with fewer high-quality neoantigens. Thus, we submit evidence that that the human immune system naturally edits neoantigens. Furthermore, we present a model to predict how immune pressure induces cancer cell populations to evolve over time. More broadly, our results argue that the immune system fundamentally surveils host genetic changes to suppress cancer.

DOI: 10.1038/s41586-022-04735-9

Source: https://www.nature.com/articles/s41586-022-04735-9

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html