Radiochemotherapy upregulates expression of checkpoint receptors on circulating T cells

Abstract

Purpose

This study assesses changes of circulating leukocyte subpopulations and the expression of checkpoint receptors in T cells in patients undergoing radiochemotherapy.

Materials and methods

Fifty-seven patients with either esophageal cancer or cervical cancer who received radiochemotherapy were recruited into this study. Serial blood collection was carried out before and during treatments. Leukocyte subpopulations and the level of PD-1 and CTLA-4 in T cells were determined by flow cytometry. The plasma concentrations of 34 human cytokines, chemokines, and growth factors were quantified.

Results

Significant decreases of lymphocyte count and percentage of T cells and B cells were observed during radiochemotherapy. Percentages of PD-1^hi and CTLA-4^hi populations in T cells increased after treatments. Proportion of activated T cells showed no significant difference. No significant changes in the plasma concentrations of the 34 humoral mediators except mild decreases of six cytokines.

Conclusion

Elevated expression of PD-1 and CTLA-4 in T cells in patients receiving radiochemotherapy, which suggests that exhaustion-like T-cell dysfunction develops during cancer cytotoxic treatments.

Keywords:

• Radiochemotherapy
• checkpoint
• circulating T cells
• cancer

Disclosure statement

The authors declare no competing financial interests.

Additional information

Funding

This study was supported by the National Natural Science Foundation of China [Grant Numbers 81372927 and 81972975].

Notes on contributors

Deguan Li

Deguan Li is a Professor at Institute of Radiation Medicine, Chinese Academy of Medical Sciences (CAMS). His research focuses on radiation injury and protection.

Yong Guan

Yong Guan is a Doctor at Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer.

Yinping Dong

Yinping Dong is a Research Assistant in Deguan Li's laboratory.

Jing Wu

Jing Wu and Yuanyang Zhang are the graduate students in Deguan Li's laboratory.

Yuanyang Zhang

Jing Wu and Yuanyang Zhang are the graduate students in Deguan Li's laboratory.

Renxiang Chen

Renxiang Chen received her PhD in 2004. She is a Research Associate at Georgetown University.

Yun-Tien Lin

Yun-Tien Lin was a Research Assistant in Heng-Hong Li's laboratory.

Albert J. Fornace

Albert J. Fornace, Jr. is a highly cited expert in stress signaling, molecular oncology, and radiobiology.

Heng-Hong Li

Heng-Hong Li is an Assistant Professor at Georgetown University. Her research focuses on investigation of transient and long lasting impacts of radiation on functions of immune cells.

Zhiyong Yuan

ZhiyongYuan is the Director of Department of Radiotherapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer. His research focuses on physical aspects of radiation oncology.