美国宾夕法尼亚大学Marco Ruella等研究人员合作发现抗CD19嵌合抗原受体（CAR）T细胞治疗后反应和毒性的肠道微生物组相关因素。2022年3月14日，《自然—医学》杂志在线发表了这项成果。

Title: Gut microbiome correlates of response and toxicity following anti-CD19 CAR T cell therapy

Author: Smith, Melody, Dai, Anqi, Ghilardi, Guido, Amelsberg, Kimberly V., Devlin, Sean M., Pajarillo, Raymone, Slingerland, John B., Beghi, Silvia, Herrera, Pamela S., Giardina, Paul, Clurman, Annelie, Dwomoh, Emmanuel, Armijo, Gabriel, Gomes, Antonio L. C., Littmann, Eric R., Schluter, Jonas, Fontana, Emily, Taur, Ying, Park, Jae H., Palomba, Maria Lia, Halton, Elizabeth, Ruiz, Josel, Jain, Tania, Pennisi, Martina, Afuye, Aishat Olaide, Perales, Miguel-Angel, Freyer, Craig W., Garfall, Alfred, Gier, Shannon, Nasta, Sunita, Landsburg, Daniel, Gerson, James, Svoboda, Jakub, Cross, Justin, Chong, Elise A., Giralt, Sergio, Gill, Saar I., Riviere, Isabelle, Porter, David L., Schuster, Stephen J., Sadelain, Michel, Frey, Noelle, Brentjens, Renier J., June, Carl H., Pamer, Eric G., Peled, Jonathan U., Facciabene, Andrea, van den Brink, Marcel R. M., Ruella, Marco

Issue&Volume: 2022-03-14

Abstract: Anti-CD19 chimeric antigen receptor (CAR) T cell therapy has led to unprecedented responses in patients with high-risk hematologic malignancies. However, up to 60% of patients still experience disease relapse and up to 80% of patients experience CAR-mediated toxicities, such as cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome. We investigated the role of the intestinal microbiome on these outcomes in a multicenter study of patients with B cell lymphoma and leukemia. We found in a retrospective cohort (n=228) that exposure to antibiotics, in particular piperacillin/tazobactam, meropenem and imipenem/cilastatin (P-I-M), in the 4 weeks before therapy was associated with worse survival and increased neurotoxicity. In stool samples from a prospective cohort of CAR T cell recipients (n=48), the fecal microbiome was altered at baseline compared to healthy controls. Stool sample profiling by 16S ribosomal RNA and metagenomic shotgun sequencing revealed that clinical outcomes were associated with differences in specific bacterial taxa and metabolic pathways. Through both untargeted and hypothesis-driven analysis of 16S sequencing data, we identified species within the class Clostridia that were associated with day 100 complete response. We concluded that changes in the intestinal microbiome are associated with clinical outcomes after anti-CD19 CAR T cell therapy in patients with B cell malignancies.

DOI: 10.1038/s41591-022-01702-9

Source: https://www.nature.com/articles/s41591-022-01702-9