Tumor Microenvironment in Thymic Epithelial Tumors: A Narrative Review

Abstract

The tumor microenvironment (TME) is a complex and constantly changing entity. The TME consists of stromal cells, fibroblasts, endothelial cells, and innate and adaptive immune cells. Cancer development and progression occurs through this interplay between the tumor and the adjacent stroma. Cancer cells are capable of modifying their microenvironment by secreting various message-carrying molecules, such as cytokines, chemokines, and other factors. This action causes a reprogramming of the neighboring cells, which are enabled to play a crucial role in tumor survival and progression. The study of TME has many clinical implications in terms of cancer therapeutics because many new drugs, such as antibodies, kinase inhibitors, and liposome formulations that can encapsulate anti-cancer drugs, can be developed. Although chemotherapy is considered the standard of treatment for advanced disease, recent research has brought to light immunotherapy as a possible systemic alternative. However, the complex structure and function of the thymus hinders its routine use in clinical practice. The aim of this review paper is to discuss the recent advances in the investigation of the unique characteristics of the TME of thymic epithelial tumors that could possibly lead to the development of novel promising therapies.

A new gene signature associated with disulfidptosis that forecasts myasthenia gravis and suggests infiltration of immune microenvironment in thymoma patients

“…In recent times, there has been a shift in cancer treatment towards therapies that target molecules. Nevertheless, the rarity and histological heterogeneity of TET pose a challenge to new treatment development [ 42 ]. Individuals identified with TETs, irrespective of their particular histopathology, additionally exhibit an inexplicable tendency towards the emergence of autoimmune toxicity impacting the muscular or neuromuscular system [ 43 ].…”

Autoimmunity in thymic epithelial tumors: a not yet clarified pathologic paradigm associated with several unmet clinical needs

“…Interestingly, the development of immune toxicity has been associated with the response, as observed in other types of cancer ( 113 , 114 , 130 – 133 ).…”

“…In a very recent paper by Agrafiotis et al., the authors comprehensively reviewed the reliable data present in literature and summarized the current knowledge related to TME of TETs associated with a favorable or dismal prognosis ( 113 ). From these data, it was suggested that high expression of PD-L1 expression on tumor cells may be considered a marker of favorable prognosis, although this issue is controversial.…”

Thymic Epithelial Tumors: An Evolving Field

“…Other crucial tumor microenvironment components are tumor-associated macrophages (TAMs). TAMs are particularly enriched in TETs with higher TMB and in thymic carcinomas, where they are likely to exert pro-proliferative effects and facilitate tumor invasiveness [ 99 , 100 ]. TAMs within TETs express different heat shock proteins, such as HSP27 and HSP70, which contribute to tumor progression with their pro-inflammatory and anti-apoptotic functions.…”