Иммуносупрессорные особенности фенотипа стромы опухолей почки различных гистологических типов

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.Введение. Почечно-клеточная карцинома представляет собой гетерогенную группу опухолевых заболеваний, характеризующуюся высокой васкуляризированностью и иммуногенностью. Иммунотерапия совершила прорыв в лечении данной патологии, однако недостаточность выработки критериев ее применения не позволяет добиться еще больших успехов. Известно, что в успехе иммунотерапии немаловажную роль играет опухолевая строма. Среди различных гистологических типов опухолей почки строма светлоклеточного варианта почечно-клеточной карциномы изучена достаточно подробно. Однако остальные гистологические типы практически не изучены.Цель исследования — описание иммуносупрессорного фенотипа стромы опухолей почки различных гистологических типов. Материалы и методы. В исследование были включены образцы опухолей, полученные от 44 больных почечно-клеточным раком различных гистологических типов (16 образцов хромофобного, 15 образцов светлоклеточного и 13 образцов папиллярного рака почки). В исследуемых образцах иммуногистохимически проведена оценка экспрессии маркеров опухолевой стромы, а именно CD68, CD206, PU.1, CD3, IDO1 и PD-L1.Результаты. Анализ общего числа макрофагов, ассоциированных с опухолью, показал, что наименьшее их количество наблюдается в образцах хромофобного рака почки, в то время как в образцах светлоклеточного рака их количество наибольшее. Для Т-клеток отмечена похожая ситуация: наибольшее число CD3+-клеток наблюдается в светлоклеточных опухолях. В хромофобных и папиллярных опухолях их количество снижено. Также папиллярные опухоли характеризуются практически полным отсутствием экспрессии PD-L1 и IDO1 по сравнению с другими гистологическими типами опухолей почки. Также мы показали, что для PU.1 наблюдается сильная положительная корреляция его количества с локализацией, как и для CD68. Таким образом, PU.1 можно использовать в качестве общего маркера для описания стромальных макрофагов в опухолях почки.Заключение. Результаты исследования показали, что опухоли почки различных гистологических типов сильно и значимо отличаются по составу своего микроокружения. Это, несомненно, необходимо учитывать при выборе иммунной терапии в лечении данной патологии

Immunosuppressive peculiarities of stromal cells of various kidney tumor types

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