Abstract
Simple SummaryIn view of the recent advances in immunoncology, we want to reevaluate and summarize the role of the immune system in malignant pleural mesothelioma (MPM). MPM is an aggressive disease with limited treatment options and devastating prognosis. Exposure to asbestos and chronic inflammation have long been acknowledged as main risk factors. In this review, we summarize the current knowledge about local and systemic inflammation promoting pathogenesis and progression of MPM. We focus on the prognostic and predictive value of infiltrating immune cells within the tumor and its microenvironment as local inflammation on the one hand and systemic inflammatory parameters on the other. We found that suppression of the specific and activation of the unspecific immune system are essential drivers of MPM, resulting in poor patient outcome. Numerous local and systemic inflammatory parameters are promising potential biomarkers for MPM, worth further research.Malignant pleural mesothelioma (MPM) is an aggressive disease with limited treatment response and devastating prognosis. Exposure to asbestos and chronic inflammation are acknowledged as main risk factors. Since immune therapy evolved as a promising novel treatment modality, we want to reevaluate and summarize the role of the inflammatory system in MPM. This review focuses on local tumor associated inflammation on the one hand and systemic inflammatory markers, and their impact on MPM outcome, on the other hand. Identification of new biomarkers helps to select optimal patient tailored therapy, avoid ineffective treatment with its related side effects and consequently improves patient’s outcome in this rare disease. Additionally, a better understanding of the tumor promoting and tumor suppressing inflammatory processes, influencing MPM pathogenesis and progression, might also reveal possible new targets for MPM treatment. After reviewing the currently available literature and according to our own research, it is concluded that the suppression of the specific immune system and the activation of its innate counterpart are crucial drivers of MPM aggressiveness translating to poor patient outcome.
Highlights
Malignant pleural mesothelioma (MPM) is an aggressive neoplasm of mesothelial origin
Our adaptive immune system is protective against cancer development and spread [27], but it is well documented that the immune system plays a crucial tumor promoting role in eventually all steps of malignant evolution by contributing to carcinogenesis, proliferation, angiogenesis, local infiltration and metastatic progression as reviewed by Coussens and Werb [28]
As possible explanation for low Dendritic Cells (DC) numbers they suggest the high levels of Interleukin-6 (IL-6) produced by MPM cells, since IL-6 inhibits the differentiation of progenitor cells to DC [51]
Summary
Malignant pleural mesothelioma (MPM) is an aggressive neoplasm of mesothelial origin. Local inflammation and immune cell infiltration within the tumor nests as well as the surrounding tumor microenvironment (TME) strongly influence the development and progression of numerous malignant diseases [23,24] including MPM as reviewed by Hendry et al [25]. Rarer detectable myeloid derived suppressor cells (MDSC) [35,36], natural killer (NK) cells [28,31,32] and regulatory T cells (Treg) [29,36,37] have been studied before These different immune cells infiltrating the tumor tissue and contributing to the TME will be summarized in the following paragraphs as well as in Table 1 with regard to their role on MPM outcome and treatment response
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