Analysis of Prostate Cancer Tumor Microenvironment Identifies Reduced Stromal CD4 Effector T-cell Infiltration in Tumors with Pelvic Nodal Metastasis.

Ntala, Chara; Salji, Mark; Salmond, Jonathan; Officer, Leah; Teodosio, Ana Vieira; Blomme, Arnaud; McGhee, Ewan J; Powley, Ian; Ahmad, Imran; Kruithof-de Julio, Marianna; Thalmann, George; Roberts, Ed; Goodyear, Carl S; Jamaspishvili, Tamara; Berman, David M; Carlin, Leo M; Le Quesne, John; Leung, Hing Y (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. Elsevier 10.1016/j.euros.2021.05.001

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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.

Design setting and participants

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.

Outcome measurements and statistical analysis

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.

Results and limitations

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, p = 0.004), and was further validated as a significant predictor of nodal metastasis in the validation cohort (OR = 0.26, p < 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.

Patient summary

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:

Journal Article (Original Article)


04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Urology

UniBE Contributor:

Kruithof-de Julio, Marianna, Thalmann, George


600 Technology > 610 Medicine & health








Jeannine Wiemann

Date Deposited:

13 Oct 2021 10:37

Last Modified:

05 Dec 2022 15:53

Publisher DOI:


PubMed ID:


Uncontrolled Keywords:

Immune cells Lymph node Prostate cancer Tumor microenvironment




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