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Updated: Nov 9, 2025

Evaluation of Tumor-infiltrating Leukocyte Subsets in a Subcutaneous Tumor Model
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CDKN2A Deletion in Melanoma Excludes T Cell Infiltration by Repressing Chemokine Expression in a Cell Cycle-Dependent

Zhen Zhu1, Hao Song2, Juan Xu3

  • 1The State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center, Nanjing University, Nanjing, China.

Frontiers in Oncology
|April 12, 2021
PubMed

Insights

CDKN2A deletion inhibits T-cell infiltration in melanoma by reducing chemokine expression. This finding impacts T-cell-based immunotherapy by highlighting a key mechanism limiting treatment efficacy in solid tumors.

Area of Science:

  • Oncology
  • Immunology
  • Cancer Genomics

Background:

  • T-cell-mediated immunity is crucial for effective T-cell-based immunotherapy.
  • Limited T-cell infiltration in solid tumors hinders the therapeutic potential of these treatments.

Purpose of the Study:

  • To investigate the molecular and genetic factors influencing T-cell infiltration in cutaneous melanoma.
  • To identify specific genetic alterations associated with reduced T-cell infiltration and their functional implications.

Main Methods:

  • Analysis of The Cancer Genome Atlas (TCGA)-skin cutaneous melanoma (SKCM) cohort for correlations between T-cell infiltration and genomic alterations.
  • Validation in independent melanoma cohorts (DFCI, TGEN).
  • Immunohistochemistry analysis of CDKN2A and CD8 expression in melanoma patient samples.
  • Gene and pathway analysis of CDKN2A deletion groups versus normal groups.
  • Mechanistic studies exploring signaling pathways involved in CDKN2A function.

Main Results:

  • T-cell infiltration negatively correlated with genome copy number alteration in TCGA-SKCM.
  • CDKN2A copy number was significantly decreased in patients with low T-cell infiltration, a finding validated in other cohorts.
  • CDKN2A expression positively correlated with CD8 expression in melanoma patients.
  • CDKN2A deletion was associated with altered gene and pathway expression, particularly in the chemokine pathway.
  • CDKN2A deletion inhibited T-cell infiltration by suppressing chemokine expression, potentially via MAPK and NF-κB pathways in a cell cycle-dependent manner.
  • CDKN2A deletion also correlated with reduced T-cell marker expression in other cancer types.

Conclusions:

  • CDKN2A deletion is a significant factor limiting T-cell infiltration in melanoma.
  • The mechanism involves the suppression of chemokine expression in a cell cycle-dependent manner.
  • These findings provide insights into overcoming immunotherapy resistance in solid tumors.
Keywords:
CDKN2AT-cell infiltrationcell cycle dependentchemokinemelanoma

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