Immunosuppressive peculiarities of stromal cells of various kidney tumor types
https://doi.org/10.17650/1726-9776-2020-16-2-29-35
Abstract
Background. Renal cell carcinoma is a heterogeneous group of tumors characterized by high vascularization and immunogenicity. Immunotherapy has made a breakthrough in the treatment of this pathology, however, the lack of development of criteria for its use does not allow to achieve even greater success. It is known that the tumor stroma plays an important role in the success of immunotherapy. Among the various histological types of kidney tumors, the stroma of the clear cell renal cell carcinoma has been studied in sufficient detail. However, the remaining histological types are practically not studied.
Objective: description of the immunosuppressive phenotype of the stroma of kidney tumors of various histological types.
Materials and methods. The study included tumor samples obtainedfrom 44patients with renal cell carcinoma of various histological types (16 samples of chromophobe cancer, 15 samples of clear cell and 13 samples of papillary renal cell carcinoma). The method of immunohis-tochemistry evaluated the expression of tumor stromal markers, namely CD68, CD206, PU.1, CD3, IDO1 and PD-L1 in the studied samples.
Results. Analysis of the total number of macrophages associated with the tumor showed that the smallest number is observed in samples of chromophobe renal cancer, while in the samples of clear cell cancer their number is greatest. A similar situation is observed for T-cells: the largest number of CD3+ cells is observed in clear cell tumors. In chromophobe and papillary tumors, their number is reduced. Papillary tumors are also characterized by an almost complete absence of expression of PD-L1 and IDO1 compared to other histological types of kidney tumors. We also showed that for PU.1 there is a strong positive correlation between its quantity and localization, as in CD68. Thus, PU.1 can be used as a general marker for describing stromal macrophages in kidney tumors.
Conclusion. The study showed that kidney tumors of various histological types strongly and significantly differ in the composition of their microenvironment. These data, of course, must be considered when choosing immune therapy in the treatment of this pathology.
Keywords
About the Authors
O. V. KovalevaRussian Federation
24 Kashirskoe Shosse, Moscow 115478
Competing Interests: not
M. A. Rashidova
Russian Federation
24 Kashirskoe Shosse, Moscow 115478
Competing Interests: not
D. V. Samoilova
Russian Federation
24 Kashirskoe Shosse, Moscow 115478
Competing Interests: not
P. A. Podlesnaya
Russian Federation
24 Kashirskoe Shosse, Moscow 115478
Competing Interests: not
R. M. Tabiev
24 Kashirskoe Shosse, Moscow 115478; 23 Academika Scriabina St., Moscow 109472
Competing Interests: not
N. V. Kuntsevich
Build. 1, 513rd Parkovaya St., Moscow 105425
Competing Interests: not
G. D. Efremov
Build. 1, 513rd Parkovaya St., Moscow 105425
Competing Interests: not
B. Ya. Alekseev
Build. 1, 513rd Parkovaya St., Moscow 105425
Competing Interests: not
A. N. Gratchev
Russian Federation
24 Kashirskoe Shosse, Moscow 115478;
Build. 1, 513rd Parkovaya St., Moscow 105425
Competing Interests: not
References
1. Hsieh J.J., Purdue M.P., Signoretti S., et al. Renal cell carcinoma. Nat Rev Dis Primers. 2017;3:17009. DOI:10.1038/nrdp.2017.9. PMID:PMC5936048.
2. Kovaleva O.V., Samoilova D.V., Shitova M.S., et al. Tumor Associated Macrophages in Kidney Cancer. Anal Cell Pathol (Amst). 2016;2016:9307549. DOI:10.1155/2016/9307549. PMID:PMC5078639.
3. Gratchev A., Kzhyshkowska J., Utikal J., et al. Interleukin-4 and dexamethasone counterregulate extracellular matrix remodelling and phagocytosis in type-2 macrophages. Scandinavian journal of immunology. 2005;61(1):10-7. DOI:10.1111/j.0300-9475.2005.01524.x.
4. Holness C.L., Simmons D.L. Molecular cloning of CD68, a human macrophage marker related to lysosomal glycoproteins. Blood. 1993;81(6):1607-13.
5. Mak K.S., Funnell A.P., Pearson R.C., et al. PU.1 and Haematopoietic Cell Fate: Dosage Matters. Int J Cell Biol. 2011;2011:808524. DOI:10.1155/2011/808524. PMID:PMC3154517.
6. Jiang X., Wang J., Deng X., et al. Role of the tumor microenvironment in PD-L1/PD-1-mediated tumor immune escape. Molecular cancer. 2019;18(1):10. DOI:10.1186/s12943-018-0928-4. PMID:PMC6332843.
7. Cohen H.T., McGovern F.J. Renal-cell carcinoma. The New England journal of medicine. 2005;353(23):2477-90. DOI:10.1056/NEJMra043172.
8. Choueiri T.K. Renal cell carcinoma. Hematol Oncol Clin North Am. 2011;25(4):xiii-xiv. DOI:10.1016/j.hoc.2011.06.001.
9. Chevrier S., Levine J.H., Zanotelli V.R.T., et al. An Immune Atlas of Clear Cell Renal Cell Carcinoma. Cell. 2017;169(4):736-49 e18. DOI:10.1016/j.cell.2017.04.016. PMID:PMC5422211.
10. Duray A., Demoulin S., Hubert P., et al. Immune suppression in head and neck cancers: a review. Clinical & developmental immunology. 2010;2010:701657. DOI:10.1155/2010/701657. PMID:PMC3061296.
11. Gratchev A., Schledzewski K., Guillot P., et al. Alternatively activated antigen-presenting cells: molecular repertoire, immune regulation, and healing. Skin pharmacology and applied skin physiology. 2001;14(5):272-9. DOI:56357.
12. Hao N.B., Lu M.H., Fan Y.H., et al. Macrophages in tumor microenvironments and the progression of tumors. Clinical & developmental immunology. 2012;2012:948098. DOI:10.1155/2012/948098. PMID:PMC3385963.
13. Geissler K., Fornara P., Lautenschlager C., et al. Immune signature of tumor infiltrating immune cells in renal cancer. Oncoimmunology. 2015;4(1):e985082. DOI:10.4161/2162402X.2014.985082. PMID:PMC4368143.
14. Thompson R.H., Gillett M.D., Cheville J.C., et al. Costimulatory B7-H1 in renal cell carcinoma patients: Indicator of tumor aggressiveness and potential therapeutic target. Proceedings of the National Academy of Sciences of the United States of America. 2004;101(49):17174-9. DOI:10.1073/pnas.0406351101. PMID:534606.
15. Thompson R.H., Dong H., Kwon E.D. Implications of B7-H1 expression in clear cell carcinoma of the kidney for prognostication and therapy. Clinical cancer research : an official journal of the American Association for Cancer Research. 2007;13(2 Pt 2):709s-15s. DOI:10.1158/1078-0432.CCR-06-1868.
16. Choueiri T.K., Fay A.P., Gray K.P., et al. PD-L1 expression in nonclear-cell renal cell carcinoma. Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. 2014;25(11):2178-84. DOI:10.1093/annonc/mdu445. PMID:PMC4288138.
17. Seeber A., Klinglmair G., Fritz J., et al. High IDO-1 expression in tumor endothelial cells is associated with response to immunotherapy in metastatic renal cell carcinoma. Cancer science. 2018;109(5):1583-91. DOI:10.1111/cas.13560. PMID:PMC5980224.
Review
For citations:
Kovaleva O.V., Rashidova M.A., Samoilova D.V., Podlesnaya P.A., Tabiev R.M., Kuntsevich N.V., Efremov G.D., Alekseev B.Ya., Gratchev A.N. Immunosuppressive peculiarities of stromal cells of various kidney tumor types. Cancer Urology. 2020;16(2):29-35. (In Russ.) https://doi.org/10.17650/1726-9776-2020-16-2-29-35