Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Aug;43(4):539-575.
doi: 10.1007/s13402-020-00519-3. Epub 2020 Jun 2.

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

Łukasz Zadka  1 , Damian J Grybowski  2 , Piotr Dzięgiel  3
Affiliations
Review

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

Łukasz Zadka et al. Cell Oncol (Dordr). 2020 Aug.

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.

Keywords: Cancer; immune response; immune system; immunosuppression; inflammation; solid tumor.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Fig. 1.
Fig. 1.
A proposed simplified model of the association between inflammation and oncogenesis. A. Common risk factors for cancers described in the text and their proinflammatory potential. Inflammation can be triggered by risk factors for cancer and long-term exposure to these factors can lead to permanent changes in cell structure and signaling associated with neoplastic transformation. B Hypoxia and proangiogenic activity are responsible for modifying the tumor microenvironment. The secretory activity of cancer cells leads to a change in the polarization of immune cells, which increases immunosuppression and causes cancer progression
Fig. 2
Fig. 2
Chronic inflammation may predispose patients to the development of neoplasms. Long term activation of inflammatory cells leads to changes in their immunophenotype, secretory activity, function and subpopulation numbers. Discrete molecular changes in the phenotype of lymphocytes and their ongoing activation in inflammatory sites are the cause of functional exhaustion of these cells, which may lead to immune suppression and, consequently, increase the chance of neoplastic transformation
Fig. 3
Fig. 3
Cancer-associated immune suppression delays wound healing after tissue injury sustained during oncologic resection. Surgery does not always allow complete removal of the neoplasm and remnant cancer cells may aggravate immune suppression. Inherent characteristics of cancer patients may indirectly suppress the immune system – some psychological factors such as chronic stress may enhance this process. Surgery modulating immune activity has impact in a specific way. Immune responses to surgery in oncologic and nononcologic patients are compared chronologically
Fig. 4
Fig. 4
Extracellular vesicles (EVs) actively secreted by cells transport various molecules, including proteins and genetic material, that are biologically active. Communication between neoplastic and host cells using EVs may modify the metabolism of targeted cells and promote neoplastic development. Neoplastic vesicles may have immunosuppressive effects on the activity of immune cells. Specific cargo of these vesicles may promote cellular anergy and decrease the ability to present antigens by switching the immunophenotype of immune cells. Exosomes released into body fluids may facilitate biomarker discovery, with special emphasis on new markers for cancer progression and classification. As yet, little is known about molecular differences between chronic inflammation-associated cancers and sporadic cancers
Fig. 5
Fig. 5
The prognostic value of tumor-infiltrating lymphocytes (TILs) and other immune cells depends on various parameters at both cellular and tissue levels. The tumor microenvironment (TME), the extracellular matrix (ECM) and the cancer cells affect the host’s adaptive immune response. On the other hand, the subtype, immunophenotype, microanatomical location and activity of inflammatory cells in the TME shape tumor immunity, which may have a pronounced effect on the patient’s clinical condition. The figure shows known molecular and tissue features (red stars) that have prognostic value due to their effect on inflammatory cells acting in the vicinity of the tumor.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. K. T. Schultz, F. Grieder, Structure and function of the immune system. Toxicol. Pathol. 15, 262–264 (1987) - PubMed
    1. L. V. Parijs, Homeostasis and self-tolerance in the immune ssystem: Turning lymphocytes off. Science 280, 243–248 (1998) - PubMed
    1. M. Bradshaw, J. Linnoila, An overview of autoimmune and paraneoplastic encephalitides. Semin. Neurol. 38, 330–343 (2018) - PubMed
    1. J. Wu, X. Xu, E. J. Lee, A. Y. Shull, L. Pei, F. Awan, X. Wang, J. H. Choi, L. Deng, H. B. Xin, W. Zhong, J. Liang, Y. Miao, Y. Wu, L. Fan, J. Li, W. Xu, H. Shi, Phenotypic alteration of CD8+ T cells in chronic lymphocytic leukemia is associated with epigenetic reprogramming. Oncotarget 7, 40558–40570 (2016) - PMC - PubMed
    1. V. Friman, O. Winqvist, C. Blimark, P. Langerbeins, H. Chapel, F. Dhalla, Secondary immunodeficiency in lymphoproliferative malignancies. Hematol. Oncol. 34, 121–132 (2016) - PubMed

LinkOut - more resources