TGF-β signaling and the interaction between platelets and T-cells in tumor microenvironment: Foes or friends?
Introduction
Since the early era of cancer therapy, many therapeutic strategies have been applied to improve the quality of life and lifespan of patients with cancer. Understanding cell–cell interaction is important to achieve a high rate of durable response in new strategies. Here, the interaction between two specific cells, platelets and T-cells, plays a pivotal role to suppress or enhance tumor growth in cancerous tissue. Recently, platelet has known as important immune cells and T-cells have been considered as the main cell to fight cancer cells [1], [2]. Following this line, the role of platelets in the advanced stage of cancer [3] and platelet effect on T-cell infiltration [4] have been studied most extensively. Platelet α-granules contain a variety of protein factors such as transforming growth factor-β (TGF-β) [5], which seems to act as a double-edged sword in cancer suppression and progression [6] via interplay with T-cells [7].
Unfortunately, many features of cellular interaction in the tumor microenvironment (TME) are still unclear. For instance, there is no evidence about platelet function and interaction between platelets and the other immune cells such as T-cells at pre-cancer status.
Understanding the whole interaction mechanism between T-cells and other cells, including platelets in cancerous tissue, might lead to the development of an alternative therapeutic strategy and improved cancer therapy [8]. Some hypotheses like reduction of platelet activation in the vicinity of tumor vessels may result in finding a new therapeutic option in order to increase therapeutic impact [9], [10]. On the other side, platelets have a contribution in cancer progression and inducing cancer cell metastasis [11]. The relationship between T-cells and platelets seems to be a solution to improve T-cell activation and treatment efficacy.
In this review, for the first time, it will be declared that platelets as immune cells are able to help T-cells to destroy non-cancerous cells in pre-cancer status while they can suppress T-cells and stimulate tumor growth in the advanced stage of cancer. Also, the role of TGF-β signaling in different stages of cancer will be reviewed.
Section snippets
Platelets and T-cells in TME
Normal cells are located on a natural substrate. However, they might be overwhelmed by intrinsic and/or acquired factors, which lead to cellular disruption. If TME aspects constantly develop, normal cells would be turned into cancer form [12]. Cancer cells are faced with a specific cell-mediated immune response called CD8 + cytotoxic T lymphocytes (CTLs), which are great candidates for recognizing and fighting cancer cells. CD8 + T-cells and CD4 + T-cells together mediate the strongest immunity
Interaction of platelets and T-cells in pre-cancer status vs advanced stage of cancer
In broad terms, pre-cancer status is a definition implied to different factors that could lead to cellular changes and increase the risk of cancer [34]. CD4 + T-cells release special chemokines and cytokines that have an essential role in face of some pre-cancer-cells [35]. Further, it seems that inflammatory condition-induced pre-cancer status [36] could directly or indirectly activate platelets. Expression of p-selectin on the surface of endothelial cells has been considered as a factor to
TGF-β signaling in different stages of cancer
To biomedical researchers, TGF-β offers an opportunity to understand the influence of secreted factors on cancer progression or suppression. This line of research is crucial to notice that how TGF-β signaling diversely works during different stages of cancer. TGF-β signaling in pre-cancer-cells is responsible for the apoptosis process or suppressing tumor growth while in the advanced stage of cancer, TGFβ acts in a diametrically opposite way and increases tumorigenesis and metastasis [86].
Conclusion
The efficacy of platelets in promoting cancer and metastasis has been well known while many studies have suggested that platelets could be efficient in T-cell attraction to inflammatory conditions. So, different roles of platelets in pre and advanced stages of cancer are expected. We hypothesized that focusing on the role of platelets in pre-cancer state and their interaction with T-cells as main cells to fight cancer cells could lead to the development of an alternative therapeutic strategy
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgement
None
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