Dataset Information

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

ABSTRACT:

Background

Pelvic nodal metastasis in prostate cancer impacts patient outcome negatively.

Objective

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).

Conclusions

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.

SUBMITTER: Ntala C

PROVIDER: S-EPMC8317840 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Ntala Chara C Salji Mark M Salmond Jonathan J Officer Leah L Teodosio Ana Vieira AV Blomme Arnaud A McGhee Ewan J EJ Powley Ian I Ahmad Imran I Kruithof-de Julio Marianna M Thalmann George G Roberts Ed E Goodyear Carl S CS Jamaspishvili Tamara T Berman David M DM Carlin Leo M LM Le Quesne John J Leung Hing Y HY

European urology open science 20210525

<h4>Background</h4>Pelvic nodal metastasis in prostate cancer impacts patient outcome negatively.<h4>Objective</h4>To explore tumor-infiltrating immune cells as a potential predictive tool for regional lymph node (LN) metastasis.<h4>Design setting and participants</h4>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 i ...[more]

PMID: 34337530

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Project description:BACKGROUND AND AIMS: Reliable prognostic markers based on biopsy specimens of colorectal cancer (CRC) are currently missing. We hypothesize that assessment of T-cell infiltration in biopsies of CRC may predict patient survival and TNM-stage before surgery. METHODS: Pre-operative biopsies and matched resection specimens from 130 CRC patients treated from 2002-2011 were included in this study. Whole tissue sections of biopsy material and primary tumors were immunostained for pancytokeratin and CD8 or CD45RO. Stromal (s) and intraepithelial (i) T-cell infiltrates were analyzed for prediction of patient survival as well as clinical and pathological TNM-stage of the primary tumor. RESULTS: CD8 T-cell infiltration in the preoperative biopsy was significantly associated with favorable overall survival (CD8i p?=?0.0026; CD8s p?=?0.0053) in patients with primary CRC independently of TNM-stage and postoperative therapy (HR [CD8i]?=?0.55 (95% CI: 0.36-0.82), p?=?0.0038; HR [CD8s]?=?0.72 (95% CI: 0.57-0.9), p?=?0.0049). High numbers of CD8i in the biopsy predicted earlier pT-stage (p?<?0.0001) as well as absence of nodal metastasis (p?=?0.0015), tumor deposits (p?=?0.0117), lymphatic (p?=?0.008) and venous invasion (p?=?0.0433) in the primary tumor. Infiltration by CD45ROs cells was independently associated with longer survival (HR?=?0.76 (95% CI: 0.61-0.96), p?=?0.0231) and predicted absence of venous invasion (p?=?0.0025). CD8 counts were positively correlated between biopsies and the primary tumor (r?=?0.42; p?<?0.0001) and were reproducible between observers (ICC [CD8i]?=?0.95, ICC [CD8s]?=?0.75). For CD45RO, reproducibility was poor to moderate (ICC [CD45i]?=?0.16, ICC [CD45s]?=?0.49) and correlation with immune infiltration in the primary tumor was fair and non-significant (r[CD45s]?=?0.16; p?=?0.2864). For both markers, no significant relationship was observed with radiographic T-stage, N-stage or M-stage, indicating that assessment of T-cells in biopsy material can add additional information to clinical staging in the pre-operative setting. CONCLUSIONS: T-cell infiltration in pre-operative biopsy specimens of CRC is an independent favorable prognostic factor and strongly correlates with absence of nodal metastasis in the resection specimen. Quantification of CD8i is highly reproducible and allows superior prediction of clinicopathological features as compared to CD45RO. The assessment of CD8i infiltration in biopsies is recommended for prospective investigation.

Dataset Information

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

Background

Objective

Design setting and participants

Outcome measurements and statistical analysis

Results and limitations

Conclusions

Patient summary

Publications

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

Similar Datasets

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