Immunosuppressive peculiarities of stromal cells of various kidney tumor types

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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.

About the authors

O. V. Kovaleva

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

ORCID iD: 0000-0001-6132-9924

24 Kashirskoe Shosse, Moscow 115478

Russian Federation

M. A. Rashidova

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

ORCID iD: 0000-0002-3267-4232

24 Kashirskoe Shosse, Moscow 115478

Russian Federation

D. V. Samoilova

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

ORCID iD: 0000-0001-5639-0835

24 Kashirskoe Shosse, Moscow 115478

Russian Federation

P. A. Podlesnaya

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

ORCID iD: 0000-0003-2312-5546

24 Kashirskoe Shosse, Moscow 115478

Russian Federation

R. M. Tabiev

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia; Moscow State Academy of Veterinary Medicine and Biotechnology — MVA named after K.I. Scriabin

ORCID iD: 0000-0002-8732-8660

24 Kashirskoe Shosse, Moscow 115478; 23 Academika Scriabina St., Moscow 109472

N. V. Kuntsevich

N.A. Lopatkin Research Institute of Urology and Interventional Radiology — branch of the National Medical Research Radiological Center, Ministry of Health of Russia

Build. 1, 513rd Parkovaya St., Moscow 105425

G. D. Efremov

N.A. Lopatkin Research Institute of Urology and Interventional Radiology — branch of the National Medical Research Radiological Center, Ministry of Health of Russia

Build. 1, 513rd Parkovaya St., Moscow 105425

B. Ya. Alekseev

N.A. Lopatkin Research Institute of Urology and Interventional Radiology — branch of the National Medical Research Radiological Center, Ministry of Health of Russia

ORCID iD: 0000-0002-3398-4128

Build. 1, 513rd Parkovaya St., Moscow 105425

A. N. Gratchev

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia; N.A. Lopatkin Research Institute of Urology and Interventional Radiology — branch of the National Medical Research Radiological Center, Ministry of Health of Russia

Author for correspondence.
Email: alexei.gratchev@gmail.com
ORCID iD: 0000-0003-2137-1866

24 Kashirskoe Shosse, Moscow 115478; 

Build. 1, 513rd Parkovaya St., Moscow 105425

Russian Federation

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