The B7-H1 (PD-L1) T Lymphocyte-Inhibitory Molecule Is Expressed in Breast Cancer Patients with Infiltrating Ductal Carcinoma: Correlation with Important High-Risk Prognostic Factors

Abstract

B7-H1 molecule increases the apoptosis of tumor-reactive T lymphocytes and reduces their immunogenicity. Breast cancer is the second most common cause of mortality after lung cancer. Direct evidence linking B7-H1 with cancer has been shown in several malignancies; however, its expression in breast cancer has not been investigated. We used immunohistochemistry to investigate the expression of the B7-H1 molecule in 44 breast cancer specimens and to study its correlation with patients' clinicopathological parameters. The expression of B7-H1 was shown in 22 of 44 patients and was not restricted to the tumor epithelium (15 of 44, 34% in tumor cells), but was also expressed by tumor-infiltrating lymphocytes (TIL; 18 of 44, 41%). Interestingly, intratumor expression of B7-H1 was significantly associated with histologic grade III-negative (P = .012), estrogen receptor-negative (P = .036), and progesterone receptor-negative (P = .040) patients. In addition, the expression of B7-H1 in TIL was associated with large tumor size (P = .042), histologic grade III (P = .015), positivity of Her2/neu status (P = .019), and severe tumor lymphocyte infiltration (P = .001). Taken together, these data suggest that B7-H1 may be an important risk factor in breast cancer patients and may represent a potential immunotherapeutic target using monoclonal antibody against the B7-H1 molecule.

PD-L1, PD-L2 and PD-1 expression in metastatic melanoma: Correlation with tumor-infiltrating immune cells and clinical outcome

“…43 However, others did not find a correlation with poor survival 32,33 and some showed an association with poor clinicopathological factors and increased immune cell infiltrate. 30 Thus, the prognostic relevance of PD-L1 and PD-L2 expression in tumors is still controversial. We find that increased frequency of PD-L1, and in particular PD-L2 expression, by melanoma cells, but not immune cells, correlates with better overall survival.…”

“…Increased expression of PD-L1 has been found in many human carcinomas, melanomas and glioblastomas. [29][30][31][32][33][34] Its expression in the TME may be expected to reduce function of PD-1 C T cells and to have a negative impact on prognosis. 35 On the other hand, PD-L1 expression can be induced by interferons secreted in the setting of active cellular immunity and therefore may be related to better patient prognosis.…”

Targeting Molecular and Cellular Inhibitory Mechanisms for Improvement of Antitumor Memory Responses Reactivated by Tumor Cell Vaccine

“…The incorporation of B7-H1 blockade and CD4 ϩ T cell depletion into tumor cell vaccine therapy resulted in complete tumor regression and long-lasting, tumorspecific immunity. Given that aggressive forms of many human cancers express high levels of B7-H1 (45)(46)(47), and that many patients harbor elevated levels of CD4 ϩ Treg cells within their tumors (48), our studies may provide useful insights for improving immunotherapeutic approaches to treat advanced cancers in the clinical setting.…”

Targeting the PD1/PD-L1 axis in melanoma: Biological rationale, clinical challenges and opportunities

“…The finding that PD-L1 is commonly upregulated on many different tumor types including melanoma [47], ovarian cancer [48], lung cancer [49], clear cell renal carcinoma [50], urothelial carcinoma [51], squamous cell carcinomas of the head and neck [52,53], esophageal cancer [54], cervical cancer [55], breast carcinoma [56], pancreatic cancer [57], gastric cancer [58], Wilms tumor [59] and glioblastoma [60], and that PD-1 is expressed in TILs, has created an important rationale for mAb blockade of this pathway for cancer immunotherapy.…”