Naslov
Immunotherapy and tumor microenvironment

Autori
Vrbanec, Damir

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, stručni

Izvornik
Archive of Oncology, Volume 25, Suplement 1 / - , 2019, 1-1

Skup
2nd Regional Congress of Medical Oncology

Mjesto i datum
Beograd, Srbija, 16.05.2019. - 18.05.2019

Vrsta sudjelovanja
Plenarno

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
checkpoint blockade, immune-phenotype, immunotherapy, tumor microevironment

Sažetak
One of the most recent development in our understanding of cancer biology is the field of immuno-oncology. The rapidly growing field of cancer immunotherapy has developed largely as result of our increased understanding of the immune sys-tem and malignancy. Recently, cancer immunotherapy, par-ticularly immune checkpoint therapy /cytotoxic T-lympho-cyte antigen-4 (CTLA- 4), programmed cell death protein 1(PD- 1) and programmed cell death ligands (PD-L1 and PD-L2) / which have been shown to have potent immunomodulatory ef-fects through their function as negative regulators of T cell ac-tivation), has progressed and provided novel strategies for the treatment. Although this immunotherapy has very promising results, the percentage of patients who respond is limited, and the factors that determine a patient’s respond are not well under-stood. There is increasing evidence demonstrating that the dif-ferences in the results of cancer immunotherapy are attributed to the heterogeneity of the tumor microenvironment/TME/. The tu-mor microenvironment consists of tumor cells, tumor-infiltrating immune cells, cancer- associated fibroblasts, the tumor vascula-ture and the extracellular matrix. Cancer cells are able to com-municate with other cells and components of the TME through two mechanisms: the first being contact-dependent mechanism between the cancer cells and another cell or with the extracellu-lar matrix and the second being contact-independent mechanism via cytokines, growth factors and lipid mediators. Modulation of the TME is now becoming an important research goal in the field of immunotherapy. There are many potential targets for cancer therapy, these including the targeting of excessive immunoregu-lation, angiogenesis, inflammation, and tumor cell communica-tion with the extracellular matrix. The recruitment, differentia-tion and location of immune cells in the TME are variable among different tumor types, and their heterogeneity is also affected. Therefore, due to the heterogeneity if immune cells in the TME, it is considered to exist three phenotypes according to the distri-bution of immune cells: immune-inflamed phenotype, immune-excluded phenotype and immune-desert phenotype. By chang-ing the immune-phenotype the TME can be modified providing a basis for personalized immunotherapy. This can be achieved by different mechanism: with immunotherapies targeted to the TME (immune checkpoint blockade), tumor metabolism regula- tion, tumor stroma regulation or combination with chemotherapy and radiotherapy. In the future, immunotherapy may be required to be tailored for each patient with cancer according to the TME.REFERENCES:1. Chen DS, Mellman I: Elements of cancer immunity and the cancer- immune set point. Nature 541:321-330, 2017.2. Pitt J.M, Marabelle A, Eggermont A et a.: Targeting the tumor mivroenvironment: removing obstruction to anticancer immune responses and immunotherapy. Ann Oncol.27:1482-92, 20163. Duan J, Wang Y, Jiao S.: Checkpoint blockade- based immunotherapy in the context of tumor- microenvironment: Opportunities and challenges. Cancer Medicine.7:4517-29, 2018.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti

POVEZANOST RADA