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Senescent T cells are reported to be increased in patients with cancer and are poor prognostic indicators. However, the distribution of senescent T cells and their correlation with clinical features in high-grade serous ovarian cancer (HGSOC) is unknown. We detected the percentage of senescent T cells in the peripheral blood and ascites of patients with advanced HGSOC (n = 86) at diagnosis by flow cytometry. Compared with healthy donors, patients with HGSOC exhibited an accumulation of CD28−CD57+ (Tsen) CD8+ T cells in the peripheral blood and ascites. The frequency of Tsen CD8+ T cells in the peripheral blood was positively correlated with age and pretreatment serum CA125 and increased in patients with large volume ascites, whereas the frequency of Tsen CD8+ T cells in ascites was elevated in patients with lymph node metastasis. Patients with Tsen-high in ascites (>19.92%), but not in the peripheral blood, were more likely to be resistant to chemotherapy and had shorter progression-free survival. Tsen CD8+ T cells exhibited common senescence features including increased SA-β-gal activity, declines in proliferation, loss of CD27 and gain of KLRG-1, and the production of cytokines. In ascites, the percentage of Tsen CD8+ T cells was positively correlated with levels of interleukin-10 and granzyme B. This study suggests the potential of ascitic Tsen CD8+ T cells at diagnosis as a prognostic biomarker in HGSOC.

Renal cell carcinoma is a common solid tumor. PBRM1 is one of the most mutation-prone genes in clear cell renal cell carcinoma (ccRCC) with the occurrence of mutation in 40% of ccRCC patients. Mutations in PBRM1 have been correlated with the efficacy of immunotherapy. However, the mutation types of PBRM1 are not well characterized. The effects of PBRM1 expression levels in the tumor microenvironment are not well studied. In addition, the mechanism and effect of anti-PD-1 immunotherapy in ccRCC tumor microenvironments are not well clarified. In this study, using bioinformatics methods we analyzed the alternation frequency and expression levels of PBRM1 in various tumors. Next, we experimentally validated their expression levels in ccRCC tissues from human and mouse models. We attempted to clarify the mechanisms of anti-PD-1 immunotherapy in ccRCC with various PBRM1 expression levels. Our results showed that deficiency of PBRM1 protein is correlated with CD4 T cell reduction in human and mouse ccRCC tissues. We also showed that anti-PD-1 Immunotherapy can increase the infiltration of T cells in both PBRM1 high and PBRM1 low tumors but to different degrees. Our study indicates that the reduction of CD4 cells in tumor tissues with low expression of PBRM1 may explain the compromised efficacy of anti-PD-1 immunotherapy in patients with PBRM1 mutated ccRCC. Our study sheds light on the potential of PBRM1 as a therapeutic target in ccRCC.

Radiotherapy (RT) has been developed with remarkable technological advances in recent years. The accuracy of RT is dramatically improved and accordingly high dose radiation of the tumors could be precisely projected. Stereotactic radiosurgery (SRS) and stereotactic body radiotherapy (SBRT), also known as stereotactic ablative radiotherapy (SABR), are rapidly becoming the accepted practice in treating solid small sized tumors. Compared with the conventional fractionation external beam radiotherapy (EBRT), SABR with very high dose per fraction and hypo-fractionated irradiation yields convincing and satisfied therapeutic effects with low toxicity, since tumor cells could be directly ablated like radiofrequency ablation (RFA). The impressive clinical efficacy of SABR is greater than expected by the linear quadratic model and the conventional radiobiological principles, i.e., 4 Rs of radiobiology (reoxygenation, repair, redistribution, and repopulation), which may no longer be suitable for the explanation of SABR's ablation effects. Based on 4 Rs of radiobiology, 5 Rs of radiobiology emphasizes the intrinsic radiosensitivity of tumor cells, which may correlate with the responsiveness of SABR. Meanwhile, SABR induced the radiobiological alteration including vascular endothelial injury and the immune activation, which has been indicated by literature reported to play a crucial role in tumor control. However, a comprehensive review involving these advances in SABR is lacking. In this review, advances in radiobiology of SABR including the role of the 4 Rs of radiobiology and potential radiobiological factors for SABR will be comprehensively reviewed and discussed.