Treatment with anti-programmed cell death 1 (PD-1) antibody restored postoperative CD8+ T cell dysfunction by surgical stress.
Millions of patients benefit from surgery and are exposed to surgical stress. However, ample studies suggest that surgical stress contributes to tumor recurrence or distant metastases. Surgical stress suppresses CD8+ T cells (CTL) function which is vital for eliminating the malignant cells. Anti-programmed cell death 1 (PD-1) therapy is an effective and safe treatment that increases survival rate of patients with multiple cancers, however, whether anti-PD-1 therapy is able to reverse the immunosuppression following surgery remains largely unknown. Using a surgical stress mice model, we found that surgical stress reduced CD8+ T cell total numbers in the spleen and impaired CTLs function. Surgical induced CD8+ T cells had impaired anti-tumor effects in a tumor bearing models. Blockade of PD-1 with specific antibody restored CD8+ T cell numbers and secretion ability. PGE2 expression was dramatically upregulated in the postoperative serum, and anti-PD-1 together with PGE2 inhibitor restored CTLs dysfunction induced by surgery. Collectively, blockade of PD-1 with monoclonal antibody may be an effective treatment during the postoperative period for restoring surgery-induced immunosuppression.
Department of Anesthesiology, Fudan University Shanghai Cancer Center, No. 270, Dong an Road, Shanghai 200032, PR China.
Zhirong
Z
Sun
Department of Liver Surgery, Fudan University Shanghai Cancer Center, No. 270, Dong an Road, Shanghai 200032, PR China.
Anrong
A
Mao
Department of Anesthesiology, Fudan University Shanghai Cancer Center, No. 270, Dong an Road, Shanghai 200032, PR China.
Yun
Y
Wang
Department of Anesthesiology, Fudan University Shanghai Cancer Center, No. 270, Dong an Road, Shanghai 200032, PR China.
Yanjun
Y
Zhao
Department of Anesthesiology, Fudan University Shanghai Cancer Center, No. 270, Dong an Road, Shanghai 200032, PR China.
Jiawei
J
Chen
Department of Anesthesiology, Fudan University Shanghai Cancer Center, No. 270, Dong an Road, Shanghai 200032, PR China. Electronic address: pingboxush@163.com.
Pingbo
P
Xu
Department of Anesthesiology, Fudan University Shanghai Cancer Center, No. 270, Dong an Road, Shanghai 200032, PR China. Electronic address: changhongmiaosh@163.com.
Changhong
C
Miao
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015232:Dinoprostone / Q000276:immunology; D007165:Immunosuppression Therapy / Q000379:methods; D051379:Mice; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology*; D013312:Stress, Physiological / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology
D000911:Antibodies, Monoclonal; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor; D015232:Dinoprostone
CD8+ T cell proliferation; PD-1 blockade; PGE2; Surgical stress