Peripheral CX3CR1+ T cells combined with PD-1 blockade therapy potentiates the anti-tumor efficacy for lung cancer

Congcong Li; Zhen Zhang; Qianfeng Cai; Qitai Zhao; Han Wu; JunRu Li; Yaqing Liu; Xuan Zhao; Jinyan Liu; Yu Ping; Jiqi Shan; Shengli Yang; Yi Zhang

doi:10.1080/2162402X.2024.2355684

Peripheral CX3CR1⁺ T cells combined with PD-1 blockade therapy potentiates the anti-tumor efficacy for lung cancer

Oncoimmunology. 2024 May 22;13(1):2355684. doi: 10.1080/2162402X.2024.2355684. eCollection 2024.

Authors

Congcong Li¹, Zhen Zhang^{1

2}, Qianfeng Cai^{1

3}, Qitai Zhao¹, Han Wu¹, JunRu Li¹, Yaqing Liu¹, Xuan Zhao¹, Jinyan Liu¹, Yu Ping¹, Jiqi Shan¹, Shengli Yang¹, Yi Zhang^{1

2

3

4}

Affiliations

¹ Biotherapy Center & Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
² State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan, China.
³ School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, China.
⁴ Henan Key Laboratory for Tumor Immunology and Biotherapy, Zhengzhou, Henan, China.

Abstract

Identifying tumor-relevant T cell subsets in the peripheral blood (PB) has become a potential strategy for cancer treatment. However, the subset of PB that could be used to treat cancer remains poorly defined. Here, we found that the CX3CR1⁺ T cell subset in the blood of patients with lung cancer exhibited effector properties and had a higher TCR matching ratio with tumor-infiltrating lymphocytes (TILs) compared to CX3CR1^- T cells, as determined by paired single-cell RNA and TCR sequencing. Meanwhile, the anti-tumor activities, effector cytokine production, and mitochondrial function were enhanced in CX3CR1⁺ T cells both in vitro and in vivo. However, in the co-culture system of H322 cells with T cells, the percentages of apoptotic cells and Fas were substantially higher in CX3CR1⁺ T cells than those in CX3CR1^- T cells. Fas-mediated apoptosis was rescued by treatment with an anti-PD-1 antibody. Accordingly, the combination of adoptive transfer of CX3CR1⁺ T cells and anti-PD-1 treatment considerably decreased Fas expression and improved the survival of lung xenograft mice. Moreover, an increased frequency of CX3CR1⁺ T cells in the PB correlated with a better response and prolonged survival of patients with lung cancer who received anti-PD-1 therapy. These findings indicate the promising potential of adoptive transfer of peripheral CX3CR1⁺ T cells as an individual cancer immunotherapy.

Keywords: CX3CR1+ T cells; Fas; anti-PD-1 treatment; cancer immunotherapy; lung cancer.

MeSH terms

Animals
Apoptosis / drug effects
CX3C Chemokine Receptor 1* / metabolism
Cell Line, Tumor
Female
Humans
Immune Checkpoint Inhibitors* / pharmacology
Immune Checkpoint Inhibitors* / therapeutic use
Lung Neoplasms* / drug therapy
Lung Neoplasms* / immunology
Lung Neoplasms* / pathology
Lymphocytes, Tumor-Infiltrating* / drug effects
Lymphocytes, Tumor-Infiltrating* / immunology
Lymphocytes, Tumor-Infiltrating* / metabolism
Male
Mice
Programmed Cell Death 1 Receptor* / antagonists & inhibitors
Programmed Cell Death 1 Receptor* / metabolism
T-Lymphocyte Subsets / drug effects
T-Lymphocyte Subsets / immunology
T-Lymphocyte Subsets / metabolism
T-Lymphocytes / drug effects
T-Lymphocytes / immunology
T-Lymphocytes / metabolism
Xenograft Model Antitumor Assays

Substances

CX3C Chemokine Receptor 1
CX3CR1 protein, human
Immune Checkpoint Inhibitors
Programmed Cell Death 1 Receptor
PDCD1 protein, human

Grants and funding

This study was supported by the National Key R&D Program: Intergovernmental International Science and Technology Innovation Cooperation Project [Grant no. 2022YFE0141000], the National Natural Science Foundation of China [Grant nos. 82102868, 82272873], Medical Science and Technology Project of Henan Province [SBGJ202101010], Project of Central Leading Local Science and Technology Development of Henan Province [Z20221343036], Health science and Technology Innovation Outstanding Young Talents Training Project [YXKC2020051], Science and Technology project of Henan Province [242102311001, 232102311148, 232102310509]. National funded postdoctoral researcher program [GZC20232435].