Severe inherited thrombophilia includes rare deficiencies of natural anticoagulants (antithrombin and proteins C and S) and homozygous or combined factor V Leiden and FII G20210A variants. They are associated with a high thrombosis risk and can impact the duration of anticoagulation therapy for patients with a venous thromboembolism (VTE) event. Therefore, it is important to diagnose thrombophilia and to use adapted anticoagulant therapy. The widespread use of direct anticoagulants (DOACs) for VTE has raised new issues concerning inherited thrombophilia. Concerning inherited thrombophilia diagnosis, DOACs are directed toward either FIIa or FXa and can therefore interfere with coagulation assays. This paper reports DOAC interference in several thrombophilia tests, including the assessment of antithrombin, protein S, and protein C activities. Antithrombin activity and clot-based assays used for proteins C and S can be overestimated, with a risk of missing a deficiency. The use of a device to remove DOACs should be considered to minimize the risk of false-negative results. The place of DOACs in the treatment of VTE in thrombophilia patients is also discussed. Available data are encouraging, but given the variability in thrombosis risk within natural anticoagulant deficiencies, evidence in patients with well-characterized thrombophilia would be useful.

Due to the aberrant hypervascularization and the high immune infiltration of renal tumours, current therapeutic regimens of renal cell carcinoma (RCC) target angiogenic or immunosuppressive pathways or both. Tumour angiogenesis plays an essential role in tumour growth and immunosuppression. Indeed, the aberrant vasculature promotes hypoxia and can also exert immunosuppressive functions. In addition, pro-angiogenic factors, including VEGF-A, have an immunosuppressive action on immune cells. Despite the progress of treatments in RCC, there are still non responders or acquired resistance. Currently, no biomarkers are used in clinical practice to guide the choice between the different available treatments. Considering the role of angiogenesis in RCC, angiogenesis-related markers are interesting candidates. They have been studied in the response to antiangiogenic drugs (AA) and show interest in predicting the response. They have been less studied in immunotherapy alone or combined with AA. In this review, we will discuss the role of angiogenesis in tumour growth and immune escape and the place of angiogenesis-targeted biomarkers to predict response to current therapies in RCC.

Purpose: CD70 is a costimulatory molecule known to activate CD27-expressing T cells. CD27–CD70 interaction leads to the release of soluble CD27 (sCD27). Clear-cell renal cell carcinoma (ccRCC) expresses the highest levels of CD70 among all solid tumors; however, the clinical consequences of CD70 expression remain unclear. Experimental Design: Tumor tissue from 25 patients with ccRCC was assessed for the expression of CD27 and CD70 in situ using multiplex immunofluorescence. CD27+ T-cell phenotypes in tumors were analyzed by flow cytometry and their gene expression profile were analyzed by single-cell RNA sequencing then confirmed with public data. Baseline sCD27 was measured in 81 patients with renal cell carcinoma (RCC) treated with immunotherapy (35 for training cohort and 46 for validation cohort). Results: In the tumor microenvironment, CD27+ T cells interacted with CD70-expressing tumor cells. Compared with CD27− T cells, CD27+ T cells exhibited an apoptotic and dysfunctional signature. In patients with RCC, the intratumoral CD27–CD70 interaction was significantly correlated with the plasma sCD27 concentration. High sCD27 levels predicted poor overall survival in patients with RCC treated with anti–programmed cell death protein 1 in both the training and validation cohorts but not in patients treated with antiangiogenic therapy. Conclusions: In conclusion, we demonstrated that sCD27, a surrogate marker of T-cell dysfunction, is a predictive biomarker of resistance to immunotherapy in RCC. Given the frequent expression of CD70 and CD27 in solid tumors, our findings may be extended to other tumors.