High Expression of C-C Chemokine Receptor Type 5 in Urothelial Carcinoma When Compared to Other Common Malignancies Based on a Novel, Quantitative Immunohistochemistry Assay and Scoring System From FFPE Tissue not Requiring Antigen Retrieval

Main Article Content

Shaheen Alanee

Abstract

Purpose: To compare C-C chemokine receptor type 5 (CCR5) expression in urothelial carcinoma tissue to other common malignancies using a specific CCR5 inhibitor-based assay.


Methods: We used an immunohistochemistry (IHC) assay to compare the expression of  CCR5 in urothelial carcinoma to different types of common cancer. The IHC assay was based on labeled PRO140 (PRO140 CCR5 Hu IgG4a), a CCR5 inhibitor with potential therapeutic uses. The expression levels were compared using Percent Scores and H-Score methods. 


Results: Quantification of CCR5 expression utilized a panel of 63 evaluable samples from 9 cancer indications as follows: 6 UC, 7 non-small cell lung (NSCL) adenocarcinoma, 9 NSCL squamous cell carcinoma, 5 triple negative breast cancer, 5 breast cancer, 7 pancreatic cancer, 9 colorectal cancer, 7 head, and neck cancer, and 8 sarcoma. Overall, most of the 63 cases evaluated tended to have either H-Scores >175 (highly reactive) (24/63) or <100 (low or non-reactive) (32/63). Urothelial cancer had the highest expression (H score=183.3), while sarcoma exhibited the most moderate expression of CCR5 (H score =23.6).


Conclusions: We show, for the first time, a high expression of CCR5 in the tissue of urothelial carcinoma using an assay based on a safe and effective receptor inhibitor. Our findings may have therapeutic implications if validated in more extensive studies.

Article Details

How to Cite
ALANEE, Shaheen. High Expression of C-C Chemokine Receptor Type 5 in Urothelial Carcinoma When Compared to Other Common Malignancies Based on a Novel, Quantitative Immunohistochemistry Assay and Scoring System From FFPE Tissue not Requiring Antigen Retrieval. Medical Research Archives, [S.l.], v. 11, n. 11, nov. 2023. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/4620>. Date accessed: 22 dec. 2024. doi: https://doi.org/10.18103/mra.v11i11.4620.
Section
Research Articles

References

1. Coussens LM, Werb Z. Inflammation and cancer. Nature. Dec 19-26 2002;420(6917):860-7. doi:10.1038/nature01322
2. Andrews B, Shariat SF, Kim JH, Wheeler TM, Slawin KM, Lerner SP. Preoperative plasma levels of interleukin-6 and its soluble receptor predict disease recurrence and survival of patients with bladder cancer. J Urol. Mar 2002;167(3):1475-81.
3. McMillan DC, Scott HR, Watson WS, Preston T, Milroy R, McArdle CS. Longitudinal study of body cell mass depletion and the inflammatory response in cancer patients. Nutr Cancer. 1998;31(2):101-5. doi:10.1080/01635589809514687
4. Yuen KC, Liu LF, Gupta V, et al. High systemic and tumor-associated IL-8 correlates with reduced clinical benefit of PD-L1 blockade. Nat Med. May 2020;26(5):693-698. doi:10.1038/s41591-020-0860-1
5. Homey B, Muller A, Zlotnik A. Chemokines: agents for the immunotherapy of cancer? Nat Rev Immunol. Mar 2002;2(3):175-84. doi:10.1038/nri748
6. Rani A, Dasgupta P, Murphy JJ. Prostate Cancer: The Role of Inflammation and Chemokines. Am J Pathol. Nov 2019;189(11):2119-2137. doi:10.1016/j.ajpath.2019.07.007
7. Samadi M, Kamrani A, Nasiri H, et al. Cancer immunotherapy focusing on the role of interleukins: A comprehensive and updated study. Pathol Res Pract. Sep 2023;249:154732. doi:10.1016/j.prp.2023.154732
8. Vaday GG, Peehl DM, Kadam PA, Lawrence DM. Expression of CCL5 (RANTES) and CCR5 in prostate cancer. Prostate. Feb 1 2006;66(2):124-34. doi:10.1002/pros.20306
9. Singh SK, Mishra MK, Rivers BM, Gordetsky JB, Bae S, Singh R. Biological and Clinical Significance of the CCR5/CCL5 Axis in Hepatocellular Carcinoma. Cancers (Basel). Apr 5 2020;12(4)doi:10.3390/cancers12040883
10. Samson M, Stordeur P, Labbe O, Soularue P, Vassart G, Parmentier M. Molecular cloning and chromosomal mapping of a novel human gene, ChemR1, expressed in T lymphocytes and polymorphonuclear cells and encoding a putative chemokine receptor. Eur J Immunol. Dec 1996;26(12):3021-8. doi:10.1002/eji.1830261230
11. Velasco-Velazquez M, Jiao X, De La Fuente M, et al. CCR5 antagonist blocks metastasis of basal breast cancer cells. Cancer Res. Aug 1 2012;72(15):3839-50. doi:10.1158/0008-5472.CAN-11-3917
12. Sicoli D, Jiao X, Ju X, et al. CCR5 receptor antagonists block metastasis to bone of v-Src oncogene-transformed metastatic prostate cancer cell lines. Cancer Res. Dec 1 2014;74(23):7103-14. doi:10.1158/0008-5472.CAN-14-0612
13. Jiao X, Velasco-Velazquez MA, Wang M, et al. CCR5 Governs DNA Damage Repair and Breast Cancer Stem Cell Expansion. Cancer Res. Apr 1 2018;78(7):1657-1671. doi:10.1158/0008-5472.CAN-17-0915
14. Kucukgergin C, Isman FK, Dasdemir S, et al. The role of chemokine and chemokine receptor gene variants on the susceptibility and clinicopathological characteristics of bladder cancer. Gene. Dec 10 2012;511(1):7-11. doi:10.1016/j.gene.2012.09.011
15. Srivastava A, Pandey SN, Choudhuri G, Mittal B. CCR5 Delta32 polymorphism: associated with gallbladder cancer susceptibility. Scand J Immunol. May 2008;67(5):516-22. doi:10.1111/j.1365-3083.2008.02097.x
16. Jacobson JM, Thompson MA, Lalezari JP, et al. Anti-HIV-1 activity of weekly or biweekly treatment with subcutaneous PRO 140, a CCR5 monoclonal antibody. J Infect Dis. May 15 2010;201(10):1481-7. doi:10.1086/652190
17. Ward ST, Li KK, Hepburn E, et al. The effects of CCR5 inhibition on regulatory T-cell recruitment to colorectal cancer. Br J Cancer. Jan 20 2015;112(2):319-28. doi:10.1038/bjc.2014.572
18. Choi W, Porten S, Kim S, et al. Identification of distinct basal and luminal subtypes of muscle-invasive bladder cancer with different sensitivities to frontline chemotherapy. Cancer Cell. Feb 10 2014;25(2):152-65. doi:10.1016/j.ccr.2014.01.009