Bidirectional regulatory mechanisms and therapeutic prospects of tumor hypercoagulable state and immunosuppressive tumor microenvironment.

The tumor hypercoagulable state (THS) is an acquired and persistent prothrombotic condition driven by the tumor and its microenvironment. An immunosuppressive tumor microenvironment (TME) is a local microenvironment that suppresses antitumor immune responses and promotes tumor evasion of immune surveillance and is also a key driver of tumorigenesis, tumor progression, and metastasis. An intricate bidirectional regulatory axis exists between THS and immunosuppressive TME, establishing a self-reinforcing "hypercoagulability-immunosuppression" vicious cycle that severely impairs patient prognosis and reduces the efficacy of immunotherapy. To break this vicious cycle, the combined use of anticoagulant therapy and immunotherapy has garnered increasing attention. Current treatment techniques aimed at the coagulation-immune axis hold significant promise. However, this combinatorial method has a number of translational issues, including bleeding hazards, tumor heterogeneity, a lack of prognostic biomarkers, unexplained resistance mechanisms, and difficulties in clinical implementation. This review delineates the bidirectional regulatory mechanisms that link THS and immunosuppressive TME, assesses the promise of combined therapeutic modalities, discusses current challenges, and outlines future directions for precision oncology, with the ultimate goal of providing more effective cancer treatment options.