Peripheral tuberculin purified protein derivative specific T cell immunoreactivity dynamics in non-muscle invasive bladder cancer patients receiving bacillus Calmette-Guerin instillation treatment

Huangqi Duan; Weimin Xia; Ding Xu; Yingying Chen; Yu Ding; Chen Wang; Ruiming Sun; Chengcheng Yao; Shun Zhang; Yu Wu; Ping Ji; Shujun Wang; Subo Qian; Ying Wang; Haibo Shen

doi:10.3389/fonc.2022.927410

Peripheral tuberculin purified protein derivative specific T cell immunoreactivity dynamics in non-muscle invasive bladder cancer patients receiving bacillus Calmette-Guerin instillation treatment

Front Oncol. 2022 Oct 27:12:927410. doi: 10.3389/fonc.2022.927410. eCollection 2022.

Authors

Huangqi Duan¹, Weimin Xia¹, Ding Xu¹, Yingying Chen², Yu Ding¹, Chen Wang¹, Ruiming Sun², Chengcheng Yao², Shun Zhang¹, Yu Wu¹, Ping Ji², Shujun Wang², Subo Qian¹, Ying Wang², Haibo Shen¹

Affiliations

¹ Department of Urology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
² Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Abstract

Intravesical bacillus Calmette-Guerin (BCG) instillation is recommended as an adjuvant therapy for intermediate-risk and high-risk non-muscle invasive bladder cancer (NMIBC) after transurethral resection of bladder tumor (TURBt) with nearly 70% reoccurrence. In the present study, we investigated the dynamics of peripheral purified protein derivative (PPD)-specific immune responses along the treatment. Intravesical BCG instillation caused a significant increase in peripheral PPD-specific IFN-γ release of NMIBC patients, when compared to those receiving chemo-drug instillation. Through a follow-up study, we detected rapid increase in PPD-specific IFN-γ, IL-2, and IL-17A producing CD4⁺ and CD8⁺ T cells in the induction phase. Interestingly, the frequencies of PPD-specific IFN-γ and IL-2 producing CD4⁺ and CD8⁺ T cells decreased dramatically after induction treatment and were restored after BCG re-instillation, whereas IL-17A-producing T cells remained at the maintenance phase. However, we only observed that the percentages of peripheral CD8⁺ T cells were significantly higher in BCG responder patients than those in BCG refractory patients at the baseline with the potential of predicting the recurrence. A more dramatic increase in PPD-specific IFN-γ and IL-2 producing CD4⁺ and CD8⁺ T cells after one and two dose BCG instillations was observed in refractory NMIBC patients. Therefore, regional BCG instillation induced transient peripheral PPD-specific T cell responses, which could be restored through repetitive BCG instillation. Higher proportions of peripheral CD8⁺ T cells at baseline were associated with better responses to BCG instillation for the prevention of recurrence of bladder cancer.

Keywords: bacillus Calmette-Guerin; cytokine profiles; non-muscle invasive bladder cancer (NMIBC); peripheral immune responses; predictor.