Scholarlink

<p>Penile squamous cell carcinoma (PSCC) is a rare malignancy with limited understanding of the tumor immune microenvironment (TIME). The interplay between PSCC and the immune system across disease progression and HPV infection status remains poorly characterized. This study aims to assess the TIME changes from localized to advanced disease and between HPV-positive versus negative tumors to identify potential immune evasion mechanisms in advanced PSCC. scRNA-seq was performed on ten PSCC tissue samples from penile, lymph node and distant metastatic sites with four matched penile and lymph node samples to understand the cellular heterogeneity within PSCC tumors. Analysis of immune cell populations and transcriptional hallmarks were performed stratified by localized (pT1–3, N0) versus advanced (N1–3, M0 or any N, M1) disease states and HPV infection status. We observed significant differences in immune cell infiltration between localized and advanced PSCC disease states and by HPV status. Advanced disease states demonstrated an exhausted immune phenotype, characterized by terminally exhausted CD8<sup>+</sup> T cells, M2-like macrophages and hypoxic signature, while localized disease states demonstrated an active innate immune system characterized by increased DCs. HPV-negative tumors displayed low immune cell infiltration while HPV-positive tumors demonstrated an immune exhausted phenotype. These findings offer valuable insights into the evolving PSCC immune landscape, paving the way for the development of potential therapeutic approaches for advanced PSCC.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Progressive T cell exhaustion and predominance of aging tissue associated macrophages with advancing disease stage in penile squamous cell carcinoma

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年3月5日

查看全文
  • Hiroko Miyagi,
  • Xiaoqing Yu,
  • Taylor Peak,
  • Jasreman Dhillon,
  • Casey Le,
  • Xuefeng Wang,
  • Sean Yoder,
  • Doug Marchion,
  • Xin Lu,
  • Curtis Pettaway,
  • Carlos Moran Segura,
  • Chaomei Zhang,
  • Gabriel Roman Souza,
  • Alice Yu,
  • Logan Zemp,
  • Philippe Spiess,
  • Jad Chahoud

摘要

Penile squamous cell carcinoma (PSCC) is a rare malignancy with limited understanding of the tumor immune microenvironment (TIME). The interplay between PSCC and the immune system across disease progression and HPV infection status remains poorly characterized. This study aims to assess the TIME changes from localized to advanced disease and between HPV-positive versus negative tumors to identify potential immune evasion mechanisms in advanced PSCC. scRNA-seq was performed on ten PSCC tissue samples from penile, lymph node and distant metastatic sites with four matched penile and lymph node samples to understand the cellular heterogeneity within PSCC tumors. Analysis of immune cell populations and transcriptional hallmarks were performed stratified by localized (pT1–3, N0) versus advanced (N1–3, M0 or any N, M1) disease states and HPV infection status. We observed significant differences in immune cell infiltration between localized and advanced PSCC disease states and by HPV status. Advanced disease states demonstrated an exhausted immune phenotype, characterized by terminally exhausted CD8+ T cells, M2-like macrophages and hypoxic signature, while localized disease states demonstrated an active innate immune system characterized by increased DCs. HPV-negative tumors displayed low immune cell infiltration while HPV-positive tumors demonstrated an immune exhausted phenotype. These findings offer valuable insights into the evolving PSCC immune landscape, paving the way for the development of potential therapeutic approaches for advanced PSCC.