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The programmed death (PD) pathway is frequently present in the tumor microenvironment (TME) and suppresses tumor immunity by inhibiting the activity of tumor-infiltrating lymphocytes (TILs), particularly, CD8+ lymphocytes. PD immunotherapy involves stimulation of the immune response in the region surrounding the tumor but is insufficient to prevent tumor progression. Therefore, in this study, we examined the effects of combined PD immunotherapy with fractionated radiotherapy (RT) on antitumor immunity and tumor growth in lymphoma. The immune cell profiles of the TME, blood, and secondary lymphoid organs were determined 7 days after treatment. Four combination therapies were compared. The synergistic effects of αPD-1 mAb and fractionated RT on increased CD8+ lymphocytes in the TME, blood, and secondary lymphoid organs led to substantial tumor regression in mouse EL4 lymphoma, both locally and systemically. Fractionated RT for 4 days followed by αPD-1 mAb therapy was significantly superior to other schemes in terms of overall survival rates and curative rates in xenograft model mice. Our data indicated that substantial immune responses occurred following combination therapy with fractionated RT and αPD-1 mAb immunotherapy. Our findings provide important insights into the use of RT plus αPD-1 mAb as an efficacious combinatorial therapy. [ABSTRACT FROM AUTHOR]

To determine PD1/PDL1 expression status in triple-negative breast cancer (TNBC) at both protein and mRNA levels, and to analyze the relationship between their expression and clinical parameters of the TNBC patients. Immunohistochemistry and RNAscope were used to semi quantitively evaluate PD1/PDL1 protein and mRNA expression in 195 TNBC cases on tissue microarrays. Tumor infiltrating lymphocyte (TILs) abundance was assessed using hematoxylin-eosin staining. Both tumor cells and TILs expressed PDL1. PDL1 protein and mRNA positivity was 6.7% and 74.4% respectively in tumor cells, and 31.3% and 50.9% respectively in TILs. PDL1 protein and mRNA expressions had no significant association with patient prognosis. PD1 protein was only detected in TILs (70.3% positivity). PD1 protein expression was significantly related to PDL1 expression, higher TIL abundance, Ki-67 index, basal-like subtypes, and distant metastasis. Furthermore, it was significantly associated with longer disease free survival (P<0.001) and overall survival (P = 0.004). There was no significant association between PD1 mRNA expression and clinicopathological characteristics. PD1/PDL1 protein and mRNA expressions were inconsistent (kappa = 0.705 and 0.061, respectively). PD1 protein expression in TILs, but not PDL1 in tumor cells, was a favorable prognostic factor in TNBC. PD1/PDL1 mRNA and protein expressions were inconsistent. [ABSTRACT FROM AUTHOR]