Modeling of the immune response in the pathogenesis of solid tumors and its prognostic significance

Abstract

Background Tumor initiation and subsequent progression are usually long-term processes, spread over time and conditioned by diverse aspects. Many cancers develop on the basis of chronic inflammation; however, despite dozens of years of research, little is known about the factors triggering neoplastic transformation under these conditions. Molecular characterization of both pathogenetic states, i.e., similarities and differences between chronic inflammation and cancer, is also poorly defined. The secretory activity of tumor cells may change the immunophenotype of immune cells and modify the extracellular microenvironment, which allows the bypass of host defense mechanisms and seems to have diagnostic and prognostic value. The phenomenon of immunosuppression is also present during chronic inflammation, and the development of cancer, due to its duration, predisposes patients to the promotion of chronic inflammation. The aim of our work was to discuss the above issues based on the latest scientific insights. A theoretical mechanism of cancer immunosuppression is also proposed. Conclusions Development of solid tumors may occur both during acute and chronic phases of inflammation. Differences in the regulation of immune responses between precancerous states and the cancers resulting from them emphasize the importance of immunosuppressive factors in oncogenesis. Cancer cells may, through their secretory activity and extracellular transport mechanisms, enhance deterioration of the immune system which, in turn, may have prognostic implications.

Interplay of stromal tumor-infiltrating lymphocytes, normal colonic mucosa, cancer-associated fibroblasts, clinicopathological data and the immunoregulatory molecules of patients diagnosed with colorectal cancer

“…Contrary to this statement, we also noted a significant effect of patient age on the level of IL-2Rα expression in both tumor and its stroma. The obtained result may indicate an increasing Treg population as an effect of cellular senescence, which confirms the suppressive effect of aging on T cells [ 41 ].…”

“…Regarding CRC, the prognostically favorable TIL immunophenotype is usually associated with the expression of cytotoxic T cell markers [ 19 , 40 ], which has been well documented. The adverse effect on the prognostic value in CRC seems to depend on the suppressive impact of the tumor on the regulation of the immune response, especially in relation to T cells [ 18 , 41 , 42 ]. This tendency is confirmed by the beneficial effect of a high TIL density on the prognosis [ 20 , 43 ].…”

“…Moreover, in our analysis, we found a weak, positive impact of the patient's age on the number of CD45 + cells. Such a conclusion applies only to quantitative assessments and obviously does not exclude changes in inflammatory cell activity, which occur during the cellular senescence of inflammatory cells and may adversely affect the immune response [ 41 ]. Contrary to this statement, we also noted a significant effect of patient age on the level of IL-2Rα expression in both tumor and its stroma.…”

CFP is a prognostic biomarker and correlated with immune infiltrates in Gastric Cancer and Lung Cancer

“…The effects of tumor-infiltrating immune cells have been debated for decades, and to our knowledge, these immune cells, according to the complex signals of TME, play a dual role, potentially inhibiting, as well as promoting, malignant tumor development, though more details are subject to further research [37,38]. Our results suggested that CFP may also play an important role in the recruitment and regulation of immune infiltrating cells in gastric and lung cancers.…”

“…Therefore, it is reasonable to speculate that CFP-mediated changes in the function of immune cells, in particular, the functions of T-lymphocyte activation and neutrophil adhesion, may be closely related to immune infiltration, thereby affecting the tumor microenvironment. The effects of tumor-infiltrating immune cells have been debated for decades, and to our knowledge, these immune cells, according to the complex signals of TME, play a dual role, potentially inhibiting, as well as promoting, malignant tumor development, though more details are subject to further research 37 , 38 . Our results suggested that CFP may also play an important role in the recruitment and regulation of immune infiltrating cells in gastric and lung cancers.…”