Platelet Metabolism and Other Targeted Drugs; Potential Impact on Immunotherapy

Abstract

The role of platelets in cancer progression has been well recognized in the field of cancer biology. Emerging studies are elaborating further the additional roles and added extent that platelets play in promoting tumorigenesis. Platelets release factors that support tumor growth and also form heterotypic aggregates with tumor cells, which can provide an immune-evasive advantage. Their most critical role may be the inhibition of immune cell function that can negatively impact the body’s ability in preventing tumor establishment and growth. This review summarizes the importance of platelets in tumor progression, therapeutic response, survival, and finally the notion of immunotherapy modulation being likely to benefit from the inclusion of platelet inhibitors.

Platelet aerobic metabolism: new perspectives

“…Platelet remarkable reactivity justifies their involvement in coagulative dysfunctions and thrombotic disorders [5] . Recent evidence supports the notion that platelets can also play a pivotal role in cancer progression, promoting tumorigenesis through factor secretion and metastasis to form immune-evasive aggregates with tumour cells [6] . Platelet dysfunction appears involved in complications of type II diabetes mellitus (DM): hyperglycemia would increase platelet mitochondrial ATP content [7] , but it was also shown that platelet oxidative phosphorylation (OXPHOS) was impaired in type II DM [8] .…”

“…The rapid response rate of platelet activation involves dramatic shape changes, i.e., loss of discoid form, dynamic filopodia formation [6] . This phenomenon is significantly increased in stenosed arteries in vivo, consistent with the role of platelets in vascular disease [10] .…”

Oral hygiene might prevent cancer

“…In reciprocity, through the effect of those large amounts of factors released from platelet microparticles and exosomes with antiapoptotic plus proliferation signals and angiogenic factors, platelets reinforce tumor growth [135] . These factors additionally inhibit the immune system function that prevents tumor establishment and growth [ 136 , 137 ], and induce phenotypic changes, via epithelial-mesenchymal transition, of the tumor cells, which acquire invasiveness and thus enhance their metastatic potential [134] .…”

“…In addition, the heterotypic aggregates facilitate tumor cell survival in circulation, tumor cell arrest at the endothelium, and extravasation [138] . Likewise, platelets can aggregate with inflammatory cells perhaps providing an immune-evasive advantage [136] .…”

“…These findings suggested that targeting the platelet may represent one of the preventive effects of low-dose aspirin, but also that this could be a novel strategy to treat cancer [ 134 , 135 , 137 ], together with the notion that immunotherapy might likely to benefit from the inclusion of platelet inhibitors, not only aspirin [136] .…”