Theranostics 2021; 11(10):4699-4709. doi:10.7150/thno.54546 This issue

Research Paper

Peripheral eosinophil counts predict efficacy of anti-CD19 CAR-T cell therapy against B-lineage non-Hodgkin lymphoma

Qingzhu Jia1,2*, Diyuan Qin3,4*, Feng He1,5*, Qichao Xie1,2,6*, Zhitao Ying7*, Yajing Zhang8, Yuqin Song7, Jia-Nan Cheng1,2, Xuejiao Zuo1,2, Luxiang Xu1,2, Hongliang Fang5, Chunyan Hu1,2, Lina Peng1,2, Tao Jin5, Zixiao Shi5, Peter B. Alexander4, Yongsheng Wang3, Yarong Liu5, Weidong Han8, Jun Zhu7✉, Pin Wang9✉, Qi-Jing Li4✉, Bo Zhu1,2✉

1. Department of Oncology, Xinqiao Hospital, Army Medical University, Chongqing 400037, China.
2. Chongqing Key Laboratory of Immunotherapy, Chongqing 400037, China.
3. Department of Thoracic Oncology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu 610041, China.
4. Department of Immunology, Duke University Medical Center, Durham, NC, USA.
5. R&D Department, HRAIN Biotechnology Co. Ltd., Shanghai, China.
6. Department of Oncology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing 401120, China.
7. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing, China.
8. Department of Bio-therapeutic, The First Medical Center, Chinese PLA General Hospital, Beijing, China.
9. Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, USA; Department of Pharmaceutical Sciences and Pharmacology, University of Southern California, 3710 McClintock Ave., RTH506, Los Angeles, CA 90089, USA.
*These authors contributed equally to this work.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Citation:
Jia Q, Qin D, He F, Xie Q, Ying Z, Zhang Y, Song Y, Cheng JN, Zuo X, Xu L, Fang H, Hu C, Peng L, Jin T, Shi Z, Alexander PB, Wang Y, Liu Y, Han W, Zhu J, Wang P, Li QJ, Zhu B. Peripheral eosinophil counts predict efficacy of anti-CD19 CAR-T cell therapy against B-lineage non-Hodgkin lymphoma. Theranostics 2021; 11(10):4699-4709. doi:10.7150/thno.54546. Available from https://www.thno.org/v11p4699.htm

File import instruction

Abstract

Graphic abstract

Rationale: The onset of cytokine release syndrome (CRS) and in vivo persistence of anti-CD19 chimeric antigen receptor T (CAR-T) cells after infusion correlate with clinical responsiveness. However, there are no known baseline biomarkers that can predict the prognosis of patients with B-lineage non-Hodgkin lymphoma (B-NHL). The aim of this study was to identify blood cell populations associated with beneficial outcomes in B-NHL patients administered CAR-T cell immunotherapies.

Methods: We enumerated peripheral blood and CAR-T cells by retrospectively analyzing three CAR-T cell trials involving 65 B-NHL patients. We used a preclinical model to elucidate the eosinophil mechanism in CAR-T cell therapy.

Results: During an observation period up to 30 mo, B-NHL patients with higher baseline eosinophil counts had higher objective response rates than those with low eosinophil counts. Higher baseline eosinophil counts were also significantly associated with durable progression-free survival (PFS). The predictive significance of baseline eosinophil counts was validated in two independent cohorts. A preclinical model showed that eosinophil depletion impairs the intratumoral infiltration of transferred CAR-T cells and reduces CAR-T cell antitumor efficacy.

Conclusion: The results of this study suggest that peripheral eosinophils could serve as stratification biomarkers and a recruitment machinery to facilitate anti-CD19 CAR-T cell therapy in B-NHL patients.

Keywords: biomarker, B-NHL, CAR-T, eosinophil, infiltration