Role of microenvironmental acidity and tumor exosomes in cancer immunomodulation

Abstract

Tumor microenvironment (TME) is a complex milieu in which tumor grows, develops and progresses through a complex bi-directional cross-talk with immune-, stromal cells, and the extracellular matrix (ECM). In this context, tumor-derived exosomes (TE) drive the fate of tumor cells through a stimulatory or inhibitory role on immune system. In fact, TE can induce the apoptosis of cells of the immune surveillance, and enhance the proliferation and survival of stromal cells that sustain tumor development.However, depending on the molecular cargo, TE are also able to stimulate anti-tumor immune response.TME is mainly characterized by the acidic pH that contributes to tumor development, through multiple mechanisms. Among these, the impairment of tumor immune surveillance does occur within acidic TME, and is directly mediated by acidic pH or by molecular cargo carried by TE. Little is known about the role of TE in immunomodulation in acidic conditions. The present review summarizes the studies describing the role of microenvironmental acidity and TE in immune system modulation.

Identifying prognostic signatures in the microenvironment of prostate cancer

“…In this study, we developed the TMEscore model to predict the prognosis of PCa. Consistent with previous studies in other types of tumors (6,12), PCa patients with a high TMEscore high phenotype showed a better prognosis than those with a low TMEscore. We also evaluated the efficacy of the TMEscore on prognosis compared with other common prognostic factors.…”

“…The tumor microenvironment (TME) is the cellular environment that surrounds cancer cells. The TME is composed primarily of immune cells, mesenchymal cells, endothelial cells, inflammatory mediators, and extracellular matrix (ECM) molecules (6). Immune and stromal cells are the two major types of non-tumor cellular components in the TME (7).…”

“…In addition, increasing research has suggested that cells in the TME have clinicopathological significance in predicting patient prognosis and the therapeutic efficacy of drugs (4,5). In various malignancies, including gastric cancer and glioma, gene signatures from the TME were significantly associated with the outcomes of patients (6,12). Although the landscape of TME has been widely investigated across a range of tumor types, little evidence was revealed in PCa.…”

“…We calculated the proportion of immune cells in the TME of 477 PCa samples, based on previous findings that immune cells, especially tumor infiltrating lymphocytes, are more related to prognosis and immunotherapy efficacy compared with stromal cells (6,20). We obtained a comprehensive profile of the immune cell interactions, lineages and their effects on the overall survival (OS) of PCa patients and identified four distinct patterns of TME cell infiltration (Figure 1A).…”

Exosomes in the Tumor Microenvironment: From Biology to Clinical Applications

“…For this reason, hypoxia has been explored to increase the production of mesenchymal stem cell-derived exosomes for novel therapeutic strategies based on cell-free therapy [18,120,121]. This occurs because the hypoxia increases the L-lactate production and, therefore, reduces the pH, increasing the exosome release and uptake, contributing to the crosstalk between cancer and non-cancer cells within the TME [122][123][124].…”