Min Soon Cho

Platelets induce VISTA expression and modulate the ovarian tumor microenvironment

Immune checkpoint regulators, such as the V-domain Ig suppressor of T cell activation (VISTA), play a critical role in shaping the tumor microenvironment (TME) and facilitating immune evasion. In ovarian cancer, VISTA exhibits more abundant and consistent expression than other immune checkpoints, including Programmed Death-Ligand 1 (PD-L1). This study examined the role of platelets in the regulation of VISTA in ovarian cancer using both in vitro and in vivo models. Our findings demonstrate that platelets upregulate VISTA expression in both myeloid and tumor cells, thereby promoting an immunosuppressive TME. Elevated VISTA levels were associated with higher platelet counts and poorer clinical outcomes. These results highlight that platelet-mediated VISTA upregulation is a potential therapeutic target for improving antitumor immune responses in ovarian cancer.

The effect of platelet G proteins on platelet extravasation and tumor growth in the murine model of ovarian cancer

Abstract We and other investigators have shown that platelets promote metastasis and the growth of tumors. Our rationale for conducting this study is that platelets’ prometastatic and progrowth effects depend on a close encounter between platelets and cancer cells. This interaction occurs inside blood vessels with circulating tumor cells and outside blood vessels with cancer cells residing in the tumor parenchyma. Our hypothesis was that platelet extravasation is required for the effect of platelets on tumor growth. Platelets respond to environmental stimuli by activation of G protein–coupled receptors on their surface. We investigated the impact of various platelet G proteins on the growth of ovarian cancer tumors and platelet extravasation. We used mice with platelet-specific deficiency of Gαi2 (Gi), Gα13 (G13), or Gαq (Gq) in a syngeneic ovarian cancer model. We measured the total weight of tumor nodules resected from tumor-bearing mice. We developed methods for automated whole-slide image acquisition and unbiased computerized image analysis to quantify extravasated platelets. We compared the number of platelets inside tumor nodules of platelet G protein–deficient tumor-bearing mice. We found that deficiency of Gi and G13, but not Gq, in platelets resulted in smaller tumors compared with those in corresponding littermates. Deficiency of Gi and G13 in platelets reduced the number of extravasated platelets by >90%, but deficiency of Gq did not reduce the number of extravasated platelets significantly. The lack of Gi or G13 in platelets reduced platelet extravasation into the tumor and tumor growth.