Prognostic value of immunological components of tumor microenvironment of oncourological tumors
Oleg E. Molchanov , Dmitrii N. Maistrenko , Dmitrii A. Granov , Mikhail I. Shkolnik , Igor Yu. Lisitsyn , Andrei D. Belov , Aleksei Yu. Kneev
Urology reports (St. - Petersburg) ›› 2023, Vol. 13 ›› Issue (4) : 323 -337.
Prognostic value of immunological components of tumor microenvironment of oncourological tumors
BACKGROUND: In the last decade, the tumor microenvironment has been considered as one of the key factors determining the prognosis and nature of the necessary therapeutic interventions. Currently, there is only one validated and approved predictive model that includes microenvironment components. Several classifications of the tumor microenvironment based on the nature of the predominant cellular subpopulations have been proposed.
AIM: The aim of the study was to assess the prognostic significance of the immunological components of blood and the microenvironment, as well as to create prognostic models for oncourological tumors.
MATERIALS AND METHODS: The study used clinical data from 115 patients with kidney, bladder and prostate cancer. Immunological parameters in the tumor and blood microenvironment were evaluated in all patients. The end point of observation was the median time to progression. The influence of various parameters on long-term treatment outcomes was evaluated using the log rank and the Gehan–Wilcoxon criteria. A model of proportional hazard was used to identify the combined effect of several parameters on lifetime indicators.
RESULTS: The developed prognostic models for all studied groups include spontaneous production of three cytokines: IL-6, IL-8 and IL-10. The prognostic models for renal cell carcinoma and prostate cancer also included immunosuppressive components: MDSC and Treg. The median time to progression in patients with invasive urothelial cancer is influenced by components that contribute to tumor destruction: TNK cells and IFN-γ. In all the studied groups of patients (renal cell carcinoma, muscle-invasive urothelial cancer, prostate cancer), the median time to progression significantly differs in subgroups with different numbers of immunological risk factors for tumor microenvironment.
CONCLUSIONS: The developed prognostic models are based on modern achievements of oncoimmunology and after conducting multicenter validation studies, they can be recommended for clinical use.
renal cell carcinoma / urothelial cancer / prostate cancer / microenvironment / immuno-oncology / cancer stem cells / prognostic models
| [1] |
Yang L, Lin PS. Mechanisms that drive inflammatory tumor microenvironment, tumor heterogeneity, and metastatic progression. Semin Cancer Biol. 2017;47:185–195. DOI: 10.1016/j.semcancer.2017.08.001 |
| [2] |
Yang L., Lin P.S. Mechanisms that drive inflammatory tumor microenvironment, tumor heterogeneity, and metastatic progression // Semin Cancer Biol. 2017. Vol. 47. P. 185–195. DOI: 10.1016/j.semcancer.2017.08.001 |
| [3] |
Buoncervello M, Gabriele L, Toschi E. The Janus face of tumor microenvironment targeted by immunotherapy. Int J Mol Sci. 2019;20(17):4320. DOI: 10.3390/ijms20174320 |
| [4] |
Buoncervello M., Gabriele L., Toschi E. The Janus face of tumor microenvironment targeted by immunotherapy // Int J Mol Sci. 2019. Vol. 20, No. 17. P. 4320. DOI: 10.3390/ijms20174320 |
| [5] |
Jarosz-Biej M, Smolarczyk R, Cihon T, Kulach N. Tumor microenvironment as a “Game Changer” in cancer radiotherapy. Int J Mol Sci. 2019;20(13):3212. DOI: 10.3390/ijms20133212 |
| [6] |
Jarosz-Biej M., Smolarczyk R., Cihon T., Kulach N. Tumor microenvironment as a «Game Changer» in cancer radiotherapy // Int J Mol Sci. 2019. Vol. 20, No. 13. P. 3212. DOI: 10.3390/ijms20133212 |
| [7] |
Hanahan D, Coussens LM. Accessories to the crime: functions of cells recruited to the tumor microenvironment. Cancer Cell. 2012;21(3):309–322. DOI: 10.1016/j.ccr.2012.02.022 |
| [8] |
Hanahan D., Coussens L.M. Accessories to the crime: functions of cells recruited to the tumor microenvironment // Cancer Cell. 2012. Vol. 21, No. 3. P. 309–322. DOI: 10.1016/j.ccr.2012.02.022 |
| [9] |
Dunn GP, Old LJ, Schreiber RD. The three Es of cancer immunoediting. Annu Rev Immunol. 2004;22(1):329–360. DOI: 10.1146/annurev.immunol.22.012703.104803 |
| [10] |
Dunn G.P., Old L.J., Schreiber R.D. The three Es of cancer immunoediting // Annu Rev Immunol. 2004. Vol. 22, No. 1. P. 329–360. DOI: 10.1146/annurev.immunol.22.012703.104803 |
| [11] |
Liu S, Sun Q, Ren X. Novel strategies for cancer immunotherapy: counter-immunoediting therapy. J Hematol Oncol. 2023;16(1):38. DOI: 10.1186/s13045-023-01430-8 |
| [12] |
Liu S., Sun Q., Ren X. Novel strategies for cancer immunotherapy: counter-immunoediting therapy // J Hematol Oncol. 2023. Vol. 16, No. 1. P. 38. DOI: 10.1186/s13045-023-01430-8 |
| [13] |
Talukdar S, Bhoopathi P, Emdad L, et al. Dormancy and cancer stem cells: an enigma for cancer therapeutic targeting. Adv Cancer Res. 2019;141:43–84. DOI: 10.1016/bs.acr.2018.12.002 |
| [14] |
Talukdar S., Bhoopathi P., Emdad L., et al. Dormancy and cancer stem cells: an enigma for cancer therapeutic targeting // Adv Cancer Res. 2019. Vol. 141. P. 43–84. DOI: 10.1016/bs.acr.2018.12.002 |
| [15] |
Zeng Z, Fu M, Hu Y, et al. Regulation and signaling pathways in cancer stem cells: implication for targeted therapy for cancer. Mol Cancer. 2023;22(1):172. DOI: 10.1186/s12943-023-01877-w |
| [16] |
Zeng Z., Fu M., Hu Y., et al. Regulation and signaling pathways in cancer stem cells: implication for targeted therapy for cancer // Mol Cancer. 2023. Vol. 22, No. 1. P. 172. DOI: 10.1186/s12943-023-01877-w |
| [17] |
Locati M, Curtale G, Mantovani A. Diversity, Mechanisms and significance of macrophage plasticity. Annu Rev Pathol. 2020;15: 123–147. DOI: 10.1146/annurev-pathmechdis-012418-012718 |
| [18] |
Locati M., Curtale G., Mantovani A. Diversity, Mechanisms and significance of macrophage plasticity // Annu Rev Pathol. 2020. Vol. 15, P. 123–147. DOI: 10.1146/annurev-pathmechdis-012418-012718 |
| [19] |
Zhao L, Dong Y, Zhang Y, et al. Biophysical heterogeneity of myeloid-derived microenvironement to regulate resistance to cancer immunotherapy. Adv Drug Deliv Rev. 2022;191:114585. DOI: 10.1016/j.addr.2022.114585 |
| [20] |
Zhao L., Dong Y., Zhang Y., et al. Biophysical heterogeneity of myeloid-derived microenvironement to regulate resistance to cancer immunotherapy // Adv Drug Deliv Rev. 2022. Vol. 191. P. 114585. DOI: 10.1016/j.addr.2022.114585 |
| [21] |
Ohue Y, Nishikava H. Regulatory T (Treg) cells in cancer: can Treg cells be a new therapeutic target? Cancer Sci. 2019;110(7): 2080–2089. DOI: 10.1111/cas.14069 |
| [22] |
Ohue Y., Nishikava H. Regulatory T (Treg) cells in cancer: can Treg cells be a new therapeutic target? // Cancer Sci. 2019. Vol. 110, No. 7. P. 2080–2089. DOI: 10.1111/cas.14069 |
| [23] |
Wculek SK, Cueto FJ, Mujal AM, et al. Dendritic cells in cancer immunology and immunotherapy. Nat Rev Immunol. 2019;20(1): 7–24. DOI: 10.1038/s41577-019-0210-z |
| [24] |
Wculek S.K., Cueto F.J., Mujal A.M., et al. Dendritic cells in cancer immunology and immunotherapy // Nat Rev Immunol. 2019. Vol. 20, No. 1. P. 7–24. DOI: 10.1038/s41577-019-0210-z |
| [25] |
Wu Z, Zheng Y, Han Y, et al. CD3+CD4+CD8-(double-negative) T cells in inflammation, immune disorders and cancer. Front Immunol. 2022;13:816005. DOI: 10.3389/fimmu.2022.816005 |
| [26] |
Wu Z., Zheng Y., Han Y., et al. CD3+CD4+CD8–(double-negative) T cells in inflammation, immune disorders and cancer // Front Immunol. 2022. Vol. 13. P. 816005. DOI: 10.3389/fimmu.2022.816005 |
| [27] |
Bruchard M, Ghiringhelli F. Deciphering the roles of innate lymphoid cells in cancer. Front Immunol. 2019;10:656. DOI: 10.3389/fimmu.2019.00656 |
| [28] |
Bruchard M., Ghiringhelli F. Deciphering the roles of innate lymphoid cells in cancer // Front Immunol. 2019. Vol. 10. P. 656. DOI: 10.3389/fimmu.2019.00656 |
| [29] |
Chiossone L, Dumas PY, Vienne M, Vivier E. Natural killer cells and other innate lymphoid cells in cancer. Nat Rev Immunol. 2018;18(11):671–688. DOI: 10.1038/s41577-018-0061-z |
| [30] |
Chiossone L., Dumas P.Y., Vienne M., Vivier E. Natural killer cells and other innate lymphoid cells in cancer // Nat Rev Immunol. 2018. Vol. 18, No. 11. P. 671–688. DOI: 10.1038/s41577-018-0061-z |
| [31] |
Ostroumov D, Fekete-Drimusz N, Saborowski M, et al. CD4 and CD8 T lymphocyte interplay in controlling tumor growth. Cell Mol Life Sci. 2018;75(4):689–713. DOI: 10.1007/s00018-017-2686-7 |
| [32] |
Ostroumov D., Fekete-Drimusz N., Saborowski M., et al. CD4 and CD8 T lymphocyte interplay in controlling tumor growth // Cell Mol Life Sci. 2018. Vol. 75, No. 4. P. 689–713. DOI: 10.1007/s00018-017-2686-7 |
| [33] |
Molchanov O, Maistrenko D, Granov D, et al. Features of the microenvironment of oncourological tumors. Urology reports (St. Petersburg). 2022;12(4):313–331. DOI: 10.17816/uroved112576 |
| [34] |
Молчанов О.Е., Майстренко Д.Н., Гранов Д.А., и др. Особенности микроокружения онкоурологических опухолей // Урологические ведомости. 2022. Т. 12, № 4. C. 313–331. DOI: 10.17816/uroved112576 |
| [35] |
Pages F, Mlecnik B, Marliot F, et al. International validation of the consensus immunoscore for the classification of colon cancer: a prognostic and accuracy study. Lancet. 2018;391(1035):2128–2139. DOI: 10.1016/S0140-6736(18)30789-X |
| [36] |
Pages F., Mlecnik B., Marliot F., et al. International validation of the consensus immunoscore for the classification of colon cancer: a prognostic and accuracy study // Lancet. 2018. Vol. 391, No. 1035. P. 2128–2139. DOI: 10.1016/S0140-6736(18)30789-X |
| [37] |
Galon J, Bruni D. Approaches to treat immune hot, altered and cold tumors with combination immunotherapies. Nat Rev Drug Discov. 2019;18(3):197–218. DOI: 10.1038/s41573-018-0007-y |
| [38] |
Galon J., Bruni D. Approaches to treat immune hot, altered and cold tumors with combination immunotherapies // Nat Rev Drug Discov. 2019. Vol. 18, No. 3. P. 197–218. DOI: 10.1038/s41573-018-0007-y |
| [39] |
Klatte T, Rossi SH, Stewart GD. Prognostic factors and prognostic models for renal cell carcinoma. World J Urol. 2018;36(12): 1943–1952. DOI: 10.1007/s00345-018-2309-4 |
| [40] |
Klatte T., Rossi S.H., Stewart G.D. Prognostic factors and prognostic models for renal cell carcinoma // World J Urol. 2018. Vol. 36, No. 12. P. 1943–1952. DOI: 10.1007/s00345-018-2309-4 |
| [41] |
Molchanov O, Maistrenko D, Granov D, Lisitsyn I. Prognostic value of tumor growth rate and biomarker dynamics in patients with renal cell carcinoma. Urology Reports (St. Petersburg). 2020;10(4): 281–291. DOI: 10.17816/uroved50899 |
| [42] |
Молчанов О.Е., Майстренко Д.Н., Гранов Д.А., Лисицын И.Ю. Прогностическое значение скорости роста опухоли и динамики биомаркеров у больных почечно-клеточным раком // Урологические ведомости. 2020. Т. 10, № 4. C. 281–291. DOI: 10.17816/uroved50899 |
| [43] |
Heng D, Xie W, Regan M, et al. Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study. J Clin Oncol. 2009;27(34):5794–5799. DOI: 10.1200/jco.2008.21.4809 |
| [44] |
Heng D., Xie W., Regan M., et al. Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study // J Clin Oncol. 2009. Vol. 27, No. 34. P. 5794–5799. DOI: 10.1200/jco.2008.21.4809 |
| [45] |
Eisenhauer E, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumors: revised RECIST guideline. Eur J Cancer. 2009;45(2):228–247. DOI: 10.1016/j.ejca.2008.10.026 |
| [46] |
Eisenhauer E., Therasse P., Bogaerts J., et al. New response evaluation criteria in solid tumors: revised RECIST guideline // Eur J Cancer. 2009. Vol. 45, No. 2. P. 228–247. DOI: 10.1016/j.ejca.2008.10.026 |
| [47] |
Khaydukov S, Baidun L, Zurochka A, Totolyan A. Standardized technology “Study of subpopulation composition of peripheral blood lymphocytes using flow cytofluorimeters-analyzers”. Medical Immunology (Russia). 2012;14(3):255–268. (In Russ.) DOI: 10.15789/1563-0625-2012-3-255-268 |
| [48] |
Хайдуков С.В., Байдун Л.А., Зурочка А.В., Тоталян А.А. Стандартизованная технология «Исследование субпопуляционного состава лимфоцитов периферической крови с применением проточных цитофлюориметров-анализаторов» // Медицинская иммунология. 2012. Т. 14, № 3. С. 255–268. DOI: 10.15789/1563-0625-2012-3-255-268 |
| [49] |
Anker J, Miller J, Taylor N, et al. From bench to bedside: how the tumor microenvironement is impacting the future of immunotherapy for renal cell carcinoma. Cells. 2021;10(11):3231. DOI: 10.3390/cells10113231 |
| [50] |
Anker J., Miller J., Taylor N., et al. From bench to bedside: how the tumor microenvironement is impacting the future of immunotherapy for renal cell carcinoma // Cells. 2021. Vol. 10, No. 11. P. 3231. DOI: 10.3390/cells10113231 |
| [51] |
Amsberg G, Alsdorf W, Karagiannis P, et al. Immunotherapy in advanced prostate cancer — light at the end of the tunnel? Int J Mol Sci. 2022;23(5):2569. DOI: 10.3390/ijms23052569 |
| [52] |
Amsberg G., Alsdorf W., Karagiannis P., et al. Immunotherapy in advanced prostate cancer — light at the end of the tunnel? // Int J Mol Sci. 2022. Vol. 23, No. 5. P. 2569. DOI: 10.3390/ijms23052569 |
| [53] |
Crispen P, Kusmartsev S. Mechanisms of immune evasion in bladder cancer. Cancer Immunol Immunother. 2020;69(1):3–14. DOI: 10.1007/s00262-019-02443-4 |
| [54] |
Crispen P., Kusmartsev S. Mechanisms of immune evasion in bladder cancer // Cancer Immunol Immunother. 2020. Vol. 69, No. 1. P. 3–14. DOI: 10.1007/s00262-019-02443-4 |
Eco-Vector
/
| 〈 |
|
〉 |