Interplay between coagulation and inflammation in cancer: Limitations and therapeutic opportunities. (January 2022)

• Record Type: Journal Article
• Authors: Bauer, Alexander T.; Gorzelanny, Christian; Gebhardt, Christoffer; Pantel, Klaus; Schneider, Stefan W.
• Is Part Of: Cancer treatment reviews. Volume 102(2022)
• Publication Date: 2022-01
• Subjects: Coagulation -- Inflammation -- Complement -- Thrombocytes -- Von Willebrand factor -- Immune checkpoint inhibitors; VWF von Willebrand factor -- ICI immune checkpoint inhibitor -- ADAMTS13 a disintegrin and metalloprotease with thrombospondin type 1 motifs, member 13 -- CAT cancer-associated thrombosis; Cancer -- Periodicals; Cancer -- Treatment -- Periodicals; Neoplasms -- therapy -- Periodicals; Cancer -- Périodiques; Cancer -- Traitement -- Périodiques; Cancer -- Treatment; Electronic journals; Periodicals; 616.99406
• DOI: 10.1016/j.ctrv.2021.102322
• Languages: English
• ISSNs: 0305-7372

Abstract

Graphical abstract: Highlights: Clinical data suggest that thrombosis limits efficacy of ICIs (e.g. anti-PD-1). Coagulation suppresses ICIs via platelets, leukocytes and the complement system. Molecular mechanisms of CAT envision future therapeutic targets to support ICIs. ICIs combined with anticoagulant LMWHs may improve clinical outcome. Abstract: Advances in understanding the molecular mechanisms of tumor progression have achieved impressive progress in the treatment of cancer and so-called immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy. Indeed, antibody-based drugs blocking immune escape of tumor cells by modulation of T cell responses are increasingly utilized for a wide range of tumor entities. Nonetheless, response rates remain limited, and the development of secondary resistance is a common problem. In addition, by increasing the immune response a variety of severe side effects are provoked. Next to autoimmune responses, activation of the complement system and skin toxicity, an increased incidence for thrombotic complications has been observed associated with an increased mortality rate. Based on this, it can be postulated that the interplay of coagulation with inflammation in the tumor microenvironment is relevant for each step in the tumor life cycle. This review focuses on the coagulation as central player fostering mechanisms associated with tumor progression. Thus, a better understanding of the molecular pathways involved in the complex interaction of circulating tumor cells, the plasmatic coagulation and immune cells may help to improve therapeutic concepts reducing mortality and morbidity associated with cancer.