OncoTargets and Therapy (Jul 2020)

Expression of PD-1 and PD-L1 on Tumor-Infiltrating Lymphocytes Predicts Prognosis in Patients with Small-Cell Lung Cancer

  • Sun C,
  • Zhang L,
  • Zhang W,
  • Liu Y,
  • Chen B,
  • Zhao S,
  • Li W,
  • Wang L,
  • Ye L,
  • Jia K,
  • Wang H,
  • Wu C,
  • He Y,
  • Zhou C

Journal volume & issue
Vol. Volume 13
pp. 6475 – 6483

Abstract

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Chenglong Sun,1– 3,* Liping Zhang,4,* Wei Zhang,4,* Yu Liu,3,5 Bin Chen,3 Sha Zhao,3 Wei Li,3 Lei Wang,3 Lingyun Ye,3 Keyi Jia,3,5 Hao Wang,3,5 Chunyan Wu,4 Yayi He,3 Caicun Zhou3 1Medical College of Soochow University, Suzhou 215123, Jiangsu, People’s Republic of China; 2Anhui No.2 Provincial People’s Hospital, Hefei 230041, Anhui, People’s Republic of China; 3Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, Shanghai 200433, People’s Republic of China; 4Pathology Department, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, Shanghai 200433, People’s Republic of China; 5Medical School, Tongji University, Shanghai 200433, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yayi HeDepartment of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, No. 507 Zhengmin Road, Shanghai 200433, People’s Republic of ChinaTel +13818828623Email [email protected] ZhouDepartment of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, No. 507 Zhengmin Road, Shanghai 200433, People’s Republic of ChinaTel +13301825532Email [email protected]: Immune therapy has shown good results in small-cell lung cancer (SCLC), but the impact of immune microenvironment of the disease is unclear. In this work, we detected expression of programmed death 1 (PD-1), PD-ligand 1 (PD-L1), and other immune biomarkers of cancer. We also analyzed the correlations between these markers and survival in SCLC.Patients and Methods: Protein expression of PD-1, PD-L1, PD-L2, CD3, CD4, CD8, and FOXP3 was analyzed in surgical tissues from 102 SCLC patients by immunohistochemistry.Results: Positive expression of PD-1 on tumor-infiltrating lymphocytes (TILs) was found in 40.2% of patients; 37.3% of patients showed positive expression of PD-L1 on TILs; and 3.9% showed positive expression of PD-L1 on tumor cells. PD-L2 protein was not expressed on tumor cells or TILs. Survival analysis showed that positive expression of PD-L1 on TILs was correlated with longer relapse-free survival (RFS) (p=0.004). Positive expression of PD-1 combined with a high ratio of lymphocytes (CD3, p=0.004; CD4, p=0.011; CD8, p=0.009; FOXP3, p=0.009) was associated with significantly better RFS than negative expression of PD-1 combined with a lower ratio of lymphocytes. Positive expression of PD-L1 combined with a high ratio of lymphocytes (CD3, p< 0.001; CD4, p=0.001; CD8, p=0.002; FOXP3, p=0.001) was associated with significantly better RFS than negative expression of PD-L1 combined with a lower ratio of lymphocytes. All patients’ stage were between I and III.Conclusion: PD-1 and PD-L1 expression might be good prognostic factors in SCLC.Keywords: small-cell lung cancer, SCLC, programmed death-1, PD-1, programmed death-ligand 1, PD-L1, programmed death-ligand 2, PD-L2, tumor-infiltrating lymphocytes, TILs

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