TP53 missense mutation is associated with increased tumor-infiltrating T cells in primary prostate cancer

Harsimar B. Kaur*, Jiayun Lu, Liana B. Guedes, Laneisha Maldonado, Logan Reitz, John R. Barber, Angelo M. De Marzo, Scott A. Tomlins, Karen S. Sfanos, Mario Eisenberger, Edward M. Schaeffer, Corinne E. Joshu, Tamara L. Lotan

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

The makeup of the tumor immune microenvironment may be associated with tumor somatic genomic alterations and plays a key role in tumor progression and response to immunotherapy. We examined the association of tumor-infiltrating T-cell density with TP53 status in surgically treated primary prostate cancer using 3 independent tissue microarray sets, including one set of tumors from grade-matched patients of European American or African American ancestry (n = 391), a retrospective case-cohort of intermediate- and high-risk patients enriched for adverse outcomes (n = 267), and a set of tumors with primary Gleason pattern 5 (n = 77). The presence of TP53 missense mutation, indicated by p53 nuclear accumulation using a genetically validated assay, was significantly associated with increased CD3+ T-cell density (median, 341 versus 231 CD3+ T cells/mm2; P =.004) in the matched European American and African American ancestry patient sets. The same association was present in patients of both ancestries when analyzed separately, despite the fact that p53 nuclear accumulation was less frequent among African American compared with European American tumors (7% versus 3%, P =.2). The validation cohorts of intermediate/high-risk and primary Gleason pattern 5 patients corroborated the association of increased CD3+ T-cell density with presence of p53 nuclear accumulation. In a pooled analysis of all sets, adjusting for clinicopathological variables, CD3+ and CD8+, but not FOXP3+, T-cell densities remained significantly higher in tumors with p53 nuclear accumulation compared with those without. TP53 mutation is associated with higher tumor-infiltrating T-cell density, which may be relevant in future clinical trials of immunotherapy in prostate cancer.

Original languageEnglish (US)
Pages (from-to)95-102
Number of pages8
JournalHuman pathology
Volume87
DOIs
StatePublished - May 2019

Keywords

  • CD3
  • CD8
  • FOXP3
  • Prostatic adenocarcinoma
  • T cells
  • TP53
  • Tumor-infiltrating lymphocytes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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