HHLA2 and PD-L1 co-expression predicts poor prognosis in patients with clear cell renal cell carcinoma
| Autor: | Qiang Hua Zhou, Sheng Meng Peng, Xu Chen, Hai Xia He, Ze An Li, Ran Yi Liu, Hai Huang, Qiong Wang, Wen Li Cai, Yi Ran Tao, Shi Rong Peng, Kai Wen Li |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Oncology Adult Male Cancer Research medicine.medical_specialty Combination therapy medicine.medical_treatment Immunology Immunoglobulins B7-H1 Antigen 03 medical and health sciences Young Adult 0302 clinical medicine PD-L1 Internal medicine medicine Immunology and Allergy Humans Stage (cooking) Carcinoma Renal Cell RC254-282 Aged Pharmacology Aged 80 and over biology business.industry Cancer Neoplasms. Tumors. Oncology. Including cancer and carcinogens Correction Immunotherapy Middle Aged medicine.disease Prognosis Clear cell renal cell carcinoma 030104 developmental biology 030220 oncology & carcinogenesis biology.protein Molecular Medicine Immunohistochemistry Female business CD8 |
| Zdroj: | Journal for Immunotherapy of Cancer Journal for ImmunoTherapy of Cancer, Vol 8, Iss 1 (2020) |
| ISSN: | 2051-1426 |
| Popis: | BackgroundAlthough clear cell renal cell carcinoma (ccRCC) is well known as a highly immunogenic tumor, only a small subset of patients could benefit from current immunotherapy, which might be due to the heterogeneity of immune microenvironment in ccRCC. So, it is meaningful to explore novel immunotherapy or combination therapy for improving therapeutic efficacy. HHLA2, a newly discovered B7 family member, is prevalently expressed in numerous tumors, including ccRCC. This study aimed to investigate the prognostic impact of HHLA2/PD-L1 co-expression and its relationship with tumor-infiltrating lymphocytes (TILs).MethodsThe expression levels of HHLA2, PD-L1, CD8, and CD4 in cancer tissues from cases (206 in the training cohort and 197 in the validation cohort) with surgically resectable primary ccRCC were evaluated by immunohistochemistry.ResultsThe positive rates of HHLA2 were much higher than those of PD-L1 in ccRCC tissues. HHLA2-positive expression was significantly associated with necrosis, microvascular invasion, advanced Fuhrman nuclear, and TNM stage and indicated a shorter progression-free survival (PFS) and overall survival (OS) in both cohorts. Moreover, patients with HHLA2/PD-L1 co-expression suffered the highest risk of disease progression and death by a significant margin. Besides, HHLA2/PD-L1 co-expression was significantly associated with a high density of CD8+and CD4+TILs. Notably, a new immune classification, based on HHLA2/PD-L1 co-expression and TILs, successfully stratified PFS and OS, especially in patients with TILs positivity.ConclusionsThe expression of HHLA2 is more frequent than PD-L1 in ccRCC. HHLA2/PD-L1 co-expression had an adverse impact on the prognoses of patients with ccRCC; this finding provides a rationale for combination immunotherapy with anti-HHLA2 and PD-L1 blockage for patients with ccRCC in the future. |
| Databáze: | OpenAIRE |
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