Role of CXCR3 signaling in response to anti-PD-1 therapyResearch in context
Xiao Han,
Ying Wang,
Jing Sun,
Tao Tan,
Xiaomin Cai,
Peinan Lin,
Yang Tan,
Bingfeng Zheng,
Biao Wang,
Jiawei Wang,
Lingyan Xu,
Zhengyi Yu,
Qiang Xu,
Xingxin Wu,
Yanhong Gu
Affiliations
Xiao Han
Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
Ying Wang
Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
Jing Sun
Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
Tao Tan
State Key Laboratory of Pharmaceutical Biotechnology and Collaborative Innovation Center of Chemistry for Life Sciences, School of Life Sciences, Nanjing University, Nanjing 210023, China
Xiaomin Cai
Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
Peinan Lin
Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
Yang Tan
State Key Laboratory of Pharmaceutical Biotechnology and Collaborative Innovation Center of Chemistry for Life Sciences, School of Life Sciences, Nanjing University, Nanjing 210023, China
Bingfeng Zheng
State Key Laboratory of Pharmaceutical Biotechnology and Collaborative Innovation Center of Chemistry for Life Sciences, School of Life Sciences, Nanjing University, Nanjing 210023, China
Biao Wang
Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
Jiawei Wang
Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
Lingyan Xu
Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
Zhengyi Yu
Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
Qiang Xu
State Key Laboratory of Pharmaceutical Biotechnology and Collaborative Innovation Center of Chemistry for Life Sciences, School of Life Sciences, Nanjing University, Nanjing 210023, China; Corresponding authors.
Xingxin Wu
State Key Laboratory of Pharmaceutical Biotechnology and Collaborative Innovation Center of Chemistry for Life Sciences, School of Life Sciences, Nanjing University, Nanjing 210023, China; Corresponding authors.
Yanhong Gu
Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China; Corresponding authors.
Background: Tumor mutations and tumor microenvironment are associated with resistance to cancer immunotherapies. However, peripheral T cell in effective anti-programmed death 1 (PD-1) antibody treatment is poorly understood. Methods: Mass spectrometry and conventional flow cytometry were used to investigate peripheral blood cells isolated from patients. Furthermore, melanoma mouse model was performed to assess the role of CXCR3 signaling in anti-PD-1 antibody treatment. Findings: We revealed a marked increase in the percentage of CXCR3+ T cells in the blood of cancer patients after the first pembrolizumab infusion. This percentage decreased after the second infusion in responsive patients, whereas a sustained high percentage of CXCR3+ T cells was observed in patients with progressive disease. A low percentage of CXCR3+ T cells presented in patients with stable disease or a partial response was confirmed by conventional flow cytometry. Intriguingly, blockade of CXCR3 signaling exacerbated tumor growth in mice. Intratumoral injection with recombinant CXCL9/10 plus intraperitoneal injection of anti-PD1 antibody inhibited the tumor growth in mice. Interpretation: The dynamic changes in CXCR3+ T cells in blood may be a prognostic factor in anti-PD-1 immunotherapy, and promotion of CXCR3-mediated signaling may be beneficial to the anti-PD-1 therapy. Fund: This work was supported by the National Natural Science Foundation of China (Nos. 81722047, 81871944, 81670553, 81874317, 81572389, 81730100) and Jiangsu province key medical talents (Nos. ZDRCA2016026), The “Deng Feng” Distinguished Scholars Program, National Science & Technology Major Project “Key New Drug Creation and Manufacturing Program”, China (Number: 2018ZX09201002), and the Fundamental Research Funds for the Central Universities (020814380117). Keywords: Anti-PD-1, CXCR3, Biomarker, Immunotherapy
