Immunological microenvironment in colon cancer patients with different phenotypes of cancer stem cells

Autor: Elena Yu Zlatnik, Inna A. Novikova, Elena P. Ulianova, Elena S. Bondarenko, Yuriy A. Gevorkyan, Natalya V. Soldatkina, Dmitriy S. Petrov, Vladimir E. Kolesnikov, Dmitriy A. Savchenko, Roman E. Tolmakh, Andrey V. Dashkov, Oksana V. Katelnitskaya, Sergei A. Ilchenko, Elena A. Dzhenkova, Aleksandr V. Snezhko, Evgeniy N. Kolesnikov, Aleksandr V. Shaposhnikov, Oleg I. Kit, Aleksey Yu. Maksimov
Rok vydání: 2022
Předmět:
Zdroj: Journal of Clinical Oncology. 40:e15503-e15503
ISSN: 1527-7755
0732-183X
Popis: e15503 Background: The purpose of this study was to analyze the effect of the CD44+ and CD133+ co-expression in cancer stem cells (CSCs) on lymphocytic microenvironment of colon cancer (CC). Methods: 200 CC patients received surgery as the first stage of treatment. The percentage of CSCs with the expression of CD44+ and/or CD133+ markers was studied in the tumor homogenates by flow cytometry, as well as some indicators of local immunity (CD3+, CD4+, CD8+, T regs (CD4+CD25+CD127dim), CD19+, PD-1, PD-L1, Th0, Tm, CD16/56+ and immunophenotypic characteristics of tumor cells (PD-L1, MHC-ABC). Results: Gradation depending on the absence or presence of co-expression of CSC markers on tumor cells allowed identification of 11 statistically significant differences out of 17 studied parameters of tumor cells and their lymphocytic microenvironment. Co-expression of CSC markers was accompanied by higher percentage of T regs (7.3±0.4 versus 5.3±0.5%), together with lower levels of CD4+ cells. At the same time, a higher content of the total number of T-lymphocytes was noted due to CD8+ with an increase in the percentage of memory T cells and a decline in naive T lymphocytes within this subpopulation. In addition, the co-expression of CSC markers was accompanied by a lower content of PD-L1 (34.3±3.0 vs. 42.9±2.5%) on lymphocytes and its higher content on tumor cells (10.6±1.5 vs. 4.1±0.8%), while the PD-1 expression on lymphocytes was higher (38.4±3.7 versus 22.3±2.9%). The presence of CD44+CD133+ CSCs was also accompanied by lower percentage of tumor cells expressing MHC class I (60.4±4.9 vs. 79.3±7.6%), which characterized the inhibition of recognition processes, and increased levels of CD8+, perhaps, should be considered as compensatory. Conclusions: The lymphocytic microenvironment of CC in the presence of CSCs with the CD44+CD133+ immunophenotype seems to be more immunosuppressive, according to the increase in the local content of T regs and the decrease in MHC-ABC expression. Higher expression of PD-L1 on tumor cells and PD-1 on lymphocytes allows activation of the PD-1/PD-L1 interaction, which enhances the immunosuppressive and growth-stimulating properties of the tumor microenvironment, but at the same time, makes tumor cells adequate targets for immunotherapy with immune checkpoint inhibitors.
Databáze: OpenAIRE
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