Analysis of prostate cancer tumor microenvironment identifies reduced stromal CD4 effector T-cell infiltration in tumors with pelvic nodal metastasis.

Ntala, C. et al. (2021) Analysis of prostate cancer tumor microenvironment identifies reduced stromal CD4 effector T-cell infiltration in tumors with pelvic nodal metastasis. European Urology Open Science, 29, pp. 19-29. (doi: 10.1016/j.euros.2021.05.001) (PMID:34337530) (PMCID:PMC8317840)

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Abstract

Pelvic nodal metastasis in prostate cancer impacts patient outcome negatively. To explore tumor-infiltrating immune cells as a potential predictive tool for regional lymph node (LN) metastasis. We applied multiplex immunofluorescence and targeted transcriptomic analysis on 94 radical prostatectomy specimens in patients with (LN+) or without (LN-) pelvic nodal metastases. Both intraepithelial and stromal infiltrations of immune cells and differentially expressed genes (mRNA and protein levels) were correlated with the nodal status. The identified CD4 effector cell signature of nodal metastasis was validated in a comparable independent patient cohort of 184 informative cases. Patient outcome analysis and decision curve analysis were performed with the CD4 effector cell density-based signature. In the discovery cohort, both tumor epithelium and stroma from patients with nodal metastasis had significantly lower infiltration of multiple immune cell types, with stromal CD4 effector cells highlighted as the top candidate marker. Targeted gene expression analysis and confirmatory protein analysis revealed key alteration of extracellular matrix components in tumors with nodal metastasis. Of note, stromal CD4 immune cell density was a significant independent predictor of LN metastasis (odds ratio [OR] = 0.15,  = 0.004), and was further validated as a significant predictor of nodal metastasis in the validation cohort (OR = 0.26,  < 0.001). Decreased T-cell infiltrates in the primary tumor (particularly CD4 effector cells) are associated with a higher risk of LN metastasis. Future evaluation of CD4-based assays on prostate cancer diagnostic biopsy materials may improve selection of at-risk patients for the treatment of LN metastasis. In this report, we found that cancer showing evidence of cancer metastasis to the lymph nodes tends to have less immune cells present within the tumor. We conclude that the extent of immune cells present within a prostate tumor can help doctors determine the most appropriate treatment plan for individual patients.

Item Type:Articles
Additional Information:Funding/Support and role of the sponsor: CRUK (A22904, A17196, A19661, A23983).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Le Quesne, Professor John and Carlin, Dr Leo and Ahmad, Dr Imran and Leung, Professor Hing and Salji, Dr Mark and McGhee, Dr Ewan and Ntala, Dr Chara and Roberts, Dr Ed and Goodyear, Professor Carl and Salmond, Dr Jonathan
Authors: Ntala, C., Salji, M., Salmond, J., Officer, L., Teodosio, A. V., Blomme, A., McGhee, E. J., Powley, I., Ahmad, I., Kruithof-de Julio, M., Thalmann, G., Roberts, E., Goodyear, C. S., Jamaspishvili, T., Berman, D. M., Carlin, L. M., Le Quesne, J., and Leung, H. Y.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:European Urology Open Science
Publisher:Elsevier
ISSN:2666-1691
ISSN (Online):2666-1683
Published Online:25 May 2021
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in European Urology Open Science 29:19-29
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
172068Identification and Validation of New Therapeutic Targets in Enzalutamide-Resistant Prostate CancerImran AhmadCancer Research UK (CRUK)C49745/A19661Institute of Cancer Sciences