Serum sPD-1 and sPD-L1 as Biomarkers for Evaluating the Efficacy of Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer Patients

Serum PD-1/PD-L1 Levels, Tumor Expression and PD-L1 Somatic Mutations in HER2-Positive and Triple Negative Normal-Like Feline Mammary Carcinoma Subtypes

“…Results from the immunostaining analysis revealed that PD-L1 expression in TILs and cancer cells was higher in HER2-positive mammary carcinoma, as reported in humans [ 2 , 3 , 16 , 20 , 22 ], contrasting with TN mammary carcinoma tumor samples. In spite of our findings, previous studies in human breast cancer showed that PD-1 and PD-L1 positive TILs and cancer cells overexpressing PD-L1 were frequently found in triple negative breast cancer subtype [ 16 , 23 , 38 , 39 , 40 , 41 ]. These controversial results may be due to the fact that serum PD-1 levels were higher in cats with TN normal-like carcinomas compared with animals presenting HER2-positive carcinomas, indicating that sPD-1 can bind to PD-L1 attached to the cell membrane of dendritic cells, inhibiting T cell function and proliferation, as previously described [ 42 ].…”

“…The results obtained showed that cats presenting mammary carcinoma subtypes associated with more aggressive features and poor prognosis [ 31 ] (HER2-positive and TN normal-like) displayed significantly increased serum PD-1 and PD-L1 levels, as reported in humans with HER2-positive metastatic breast cancer [ 32 ], TN breast cancer [ 23 ], renal cell carcinoma [ 25 ], esophageal cancer [ 33 ], gastric cancer [ 24 ], advanced pancreatic cancer [ 34 ], lung cancer [ 35 ] and metastatic melanoma [ 36 ] correlated to shorter overall survival and tumor-free survival times [ 23 , 25 , 32 , 33 , 35 ], suggesting a conserved role of the PD-1/PD-L1 axis in both species. Moreover, as reported in humans, our findings uncovered a positive correlation between serum PD-1 and PD-L1 levels, suggesting that both molecules are co-regulated [ 23 , 34 ]. Furthermore, cats with HER2-positive or TN normal-like tumors showed a strong positive correlation between serum PD-1, PD-L1, CTLA-4 and TNF-α levels, which are immune-inhibitory molecules that downregulate T-cell immune responses, suggesting that these animals were immunosuppressed.…”

“…The less studied serum PD-1 (sPD-1) and PD-L1 (sPD-L1) levels may also play an important role in anti-tumor immune responses. Studies in patients with breast cancer, lung cancer, metastatic melanoma and renal cell carcinoma reported higher sPD-1 or sPD-L1 levels than in healthy controls, suggesting that elevated serum PD-1 and PD-L1 levels may promote immunosuppression and are therefore to be considered adverse prognostic factors [ 23 , 24 , 25 ]. Furthermore, cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) is another immune mediator that inhibits T-cell immune function, being also targeted in breast cancer.…”

Soluble forms of PD-L1 and PD-1 as prognostic and predictive markers of sunitinib efficacy in patients with metastatic clear cell renal cell carcinoma

“…13,14 A positive correlation between sPD-1 and sPD-L1 levels was described in hepatocellular carcinoma, oral, lung and triple-negative breast cancers (TNBC) indicating that sPD-1 and sPD-L1 play an important role in the occurrence and the development of malignant tumors. 14,15 Increased sPD-L1 levels were correlated with poor clinical outcomes in head and neck squamous cell carcinoma, 16 large B-cell lymphoma, 17 melanoma, 18 pancreatic 19,20 and ovarian cancers. 21 However, the prognostic role of sPD-1 seems to depend on the type of cancers, leading either to good or poor clinical outcomes.…”

“…21 However, the prognostic role of sPD-1 seems to depend on the type of cancers, leading either to good or poor clinical outcomes. For example, high plasma levels of sPD-1 have been positively associated with inflammation and poor clinical outcomes in pancreatic cancer patients, 20 in TNBC 15 and in non-small cell lung cancer, 12 while it was a favorable prognostic factor in hepatocellular carcinoma. 22 Moreover, increased sPD-1 was correlated with prolonged survival in patients with advanced EGFRmutated non-small cell lung cancer treated with erlotinib.…”