Expression of immune checkpoint genes during kidney cancer progression
https://doi.org/10.25557/2073-7998.2023.11.13-19
Abstract
Clear cell renal cell carcinoma (ccRCC) is the most common and aggressive histologic subtype of renal tumors. At the time of diagnosis, one-third of patients develop distant metastases. Significant progress in the treatment of metastatic renal cancer has been made with the advent of targeted therapies based on immune checkpoint inhibitors. However, such therapy is not always effective. Therefore, it is relevant to study the molecular mechanisms underlying resistance to therapies that promote renal cancer progression. In this study, tumor samples obtained from patients with metastatic and non-metastatic ccRCC were investigated. The expression levels of eight genes, CD274, LGALS9, PVR, TDO2, IDO1, CD276, CEACAM1 and ADAM17, were analyzed in tumor tissue compared with the corresponding histological normal tissue. Gene expression was analyzed by real-time PCR. LGALS9, TDO2 and IDO1 genes were found to be most frequently upregulated in kidney cancer. Statistically significant differences in expression levels in the studied groups were shown for CD274, PVR and CD276 genes (Mann-Whitney test, p = <0.001; 0.003; 0.004, respectively). Our findings on the molecular genetic level of tumor progression may be useful for the development of new therapeutic treatment regimens.
About the Authors
N. V. ApanovichRussian Federation
1, Moskvorechye st., Moscow, 115522
P. V. Apanovich
Russian Federation
1, Moskvorechye st., Moscow, 115522
O. A. Khalmurzaev
Russian Federation
23, Kashirskoe shosse, Moscow, 115478
V. B. Matveev
Russian Federation
23, Kashirskoe shosse, Moscow, 115478
A. A. Alimov
Russian Federation
1, Moskvorechye st., Moscow, 115522
References
1. Siegel R.L., Miller K.D., Wagle N.S., Jemal A. Cancer statistics, 2023. CA A Cancer J. Clin. 2023; 73: 17–48.
2. Ljungberg B., Albiges L., Bedke J., et al. EAU Guidelines on Renal Cell Carcinoma; 2023; ISBN 978-94-92671-19-6.
3. Merabishvili V.M., Poltorackiy A.N., Nosov A.K., Artem’eva A.S., Merabishvili E.N. Sostoyanie onkologicheskoj pomoshchi v Rossii. Rak pochki (zabolevaemost’, smertnost’, dostovernost’ ucheta, odnogodichnaya i pogodichnaya letal’nost’, gistologicheskaya struktura). CHast’ 1. [The state of oncology care in Russia. Kidney cancer (morbidity, mortality, index of accuracy, one-year and yearby-year mortality, histological structure). Part 1]. Onkourologiya [Cancer Urology]. 2021;17(2):182-194. (In Russ.) https://doi. org/10.17650/1726-9776-2021-17-2-182-194
4. Athanazio D.A., Amorim L.S., da Cunha I.W., et al. Classification of renal cell tumors – current concepts and use of ancillary tests: recommendations of the Brazilian Society of Pathology. Surg Exp Pathol 4, 4. 2021. https://doi.org/10.1186/s42047-020-00084-x.
5. Makino T., Kadomoto S., Izumi K., Mizokami A.. Epidemiology and Prevention of Renal Cell Carcinoma. Cancers (Basel). 2022; 14(16): 4059. DOI: 10.3390/cancers14164059
6. Samnani S., Sachedina F., Gupta M., et al. Mechanisms and clinical implications in renal carcinoma resistance: narrative review of immune checkpoint inhibitors. Cancer Drug Resist 2023;6:416-29. http://dx.doi.org/10.20517/cdr.2023.02
7. Lecis D., Sangaletti S., Colombo M.P., Chiodoni C. Immune Checkpoint Ligand Reverse Signaling: Looking Back to Go Forward in Cancer Therapy. Cancers (Basel). 2019;11(5):624. doi: 10.3390/cancers11050624.
8. Xu W., Atkins M.B.., McDermott DF. Checkpoint inhibitor immunotherapy in kidney cancer. Nat Rev Urol. 2020; 17: 137–150. https://doi.org/10.1038/s41585-020-0282-3.
9. Lasorsa F., di Meo N.A., Rutigliano M., et al. Immune Checkpoint Inhibitors in Renal Cell Carcinoma: Molecular Basis and Rationale for Their Use in Clinical Practice. Biomedicines. 2023; 11: 1071. https://doi.org/10.3390/biomedicines11041071
10. López de Andrés J., Griñán-Lisón C., Jiménez G., Marchal J.A.. Cancer stem cell secretome in the tumor microenvironment: a key point for an effective personalized cancer treatment. J Hematol Oncol. 2020;13(1):136. doi: 10.1186/s13045-02000966-3.
11. Munn D.H., Mellor A.L.. IDO in the tumor microenvironment: inflammation, counter-regulation, and tolerance. Trends Immunol. 2016;37(3):193–207.
12. Moar P., Tandon R. Galectin-9 as a biomarker of disease severity. Cell Immunol. 2021;361:104287. doi: 10.1016/j.cellimm.2021.104287.
13. Cai J., Wang D., Zhang G., Guo X. The role of PD-1/PD-L1 axis in treg development and function: implications for cancer immunotherapy. Onco Targets Ther. 2019; 12: 8437-8445
14. 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 Sci. 2018;109(5):15831591. doi: 10.1111/cas.13560.
15. Maier M.K., et al. The adhesion receptor CD155 determines the magnitude of humoral immune responses against orally ingested antigens. Eur. J. Immunol. 2007; 37(8): 2214–2225.
16. Liu S., Liang J., Liu Z., et al. The Role of CD276 in Cancers. Front Oncol. 2021;11:654684. doi: 10.3389/fonc.2021.654684.
17. Liao G., Wang P., Wang Y. Identification of the Prognosis Value and Potential Mechanism of Immune Checkpoints in Renal Clear Cell Carcinoma Microenvironment. Front Oncol. 2021;11:720125. doi: 10.3389/fonc.2021.720125.
18. Hoda R.S., Brogi E., Dos Anjos C.H., et al. Clinical and pathologic features associated with PD-L1 (SP142) expression in stromal tumor-infiltrating immune cells of triple-negative breast carcinoma. Mod Pathol. 2020;33(11):2221-2232. doi: 10.1038/s41379-020-0606-0.
Review
For citations:
Apanovich N.V., Apanovich P.V., Khalmurzaev O.A., Matveev V.B., Alimov A.A. Expression of immune checkpoint genes during kidney cancer progression. Medical Genetics. 2023;22(11):13-19. (In Russ.) https://doi.org/10.25557/2073-7998.2023.11.13-19