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Published on: January 3, 2013
Expression of B7 family checkpoint proteins in cervical cancer
Liju Zong1,2,3, Yu Gu1,3, Yuncan Zhou4
1Department of Gynecologic Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Abstract:
The role of programmed cell death-ligand 1 (PD-L1) in cervical cancer has been widely investigated; however, the influences of other inhibitory B7 family members are poorly understood. We investigated the expression of PD-L1, B7 homolog 3 (B7-H3), B7-H4, and V-domain Ig suppressor of T-cell activation (VISTA) and their association with the clinicopathological features and outcomes of a large cohort of 673 patients with squamous cell carcinoma or adenocarcinoma of the uterine cervix. The positivity rates for PD-L1 (combined positive score ≥1), B7-H3 in tumor cells (TCs), B7-H4 (exclusively in TCs), VISTA in immune cells (ICs), and VISTA in TCs were 57.9%, 62.8%, 44.8%, 92.6%, and 4.8%, respectively, in 606 primary cervical cancer samples. Co-expression of PD-L1 with B7-H3 in TCs and with B7-H4 and VISTA in ICs was observed in 38.8%, 25.4%, and 57.9% of samples, respectively. B7-H3 in TCs and B7-H4 and VISTA in ICs were observed in 58.1%, 46.6%, and 83.1% of PD-L1-negative samples, respectively. These proteins were observed more frequently in squamous cell carcinomas and in moderately to poorly differentiated carcinomas. VISTA (in ICs) and B7-H4 were more frequent in primary tumors than in recurrent counterparts and correlated with improved survival; in contrast, B7-H3 positivity in TCs was less frequent in primary tumors and correlated with short disease-specific survival. Co-expression of B7-H4 and VISTA in ICs was an independent predictor of favorable outcomes overall and among patients with PD-L1-negative tumors. These data indicate that B7 family proteins exhibit differing expression patterns, distributions, and prognostic implications in cervical cancer. Furthermore, the co-expression of PD-L1 with other checkpoint proteins suggests that PD-1/PD-L1 blockade combined with modulating other immune checkpoints may present a novel therapeutic approach for cervical cancer. Future studies are needed to validate prognostic values of B7 family proteins and explore their biological roles in this malignancy.
Insights
This study reveals that B7 family proteins have diverse roles in cervical cancer, with some predicting better survival and others worse. Co-expression of B7-H4 and VISTA suggests potential for novel immunotherapies beyond PD-1/PD-L1 blockade.
Area of Science:
- Oncology
- Immunology
- Cancer Biology
Background:
- Programmed cell death-ligand 1 (PD-L1) is studied in cervical cancer, but other B7 family members' roles are unclear.
- Investigating B7-H3, B7-H4, and VISTA alongside PD-L1 is crucial for understanding cervical cancer immunity.
Purpose of the Study:
- To investigate the expression of PD-L1, B7-H3, B7-H4, and VISTA in cervical cancer.
- To analyze the association of these proteins with clinicopathological features and patient outcomes.
- To explore potential novel therapeutic strategies targeting immune checkpoints in cervical cancer.
Main Methods:
- Analysis of PD-L1, B7-H3, B7-H4, and VISTA expression in 606 primary cervical cancer samples.
- Correlation of protein expression with clinicopathological features and survival data.
- Evaluation of co-expression patterns and prognostic significance.
Main Results:
- High positivity rates for PD-L1, B7-H3, B7-H4, and VISTA were observed.
- Expression patterns differed between tumor cells and immune cells, and between primary and recurrent tumors.
- B7-H4 and VISTA in immune cells correlated with improved survival, while B7-H3 in tumor cells correlated with shorter survival.
- Co-expression of B7-H4 and VISTA in immune cells independently predicted favorable outcomes, especially in PD-L1-negative tumors.
Conclusions:
- B7 family proteins exhibit distinct expression, distribution, and prognostic implications in cervical cancer.
- Co-expression of PD-L1 with other checkpoint proteins suggests combined immunotherapies may be effective.
- Further research is needed to validate prognostic values and biological roles of B7 family proteins in cervical cancer.
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