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<p>Insufficient infiltration of cytotoxic T cells into solid tumors remains a critical obstacle in cancer immunotherapy. Despite extensive efforts to comprehend the mechanisms governing this limited infiltration, few studies have focused on the evolution of T cell motility behavior after co-culture. In this study, we combined quantitative cell trajectory analysis, computational modeling, and bulk/single-cell RNA sequencing to systematically characterize the impact of cell interactions. We reveal that in a 2.5D co-culture system with multiple cancer-cell clusters, cancer-specific T cells exhibit increased directional persistence, which facilitates their efficient searching of cancer-cell clusters. Additionally, these T cells form prolonged interactions with cancer cells, which is the most crucial factor for their accumulation on cancer-cell clusters. Furthermore, post-interaction, a cancer-cell subpopulation displays immunosuppressive traits, reducing T cell attractant expression, and undergoing epithelial-to-mesenchymal transition. These findings offer valuable insights into improving immunotherapy efficacy and tackling T cell infiltration challenges in solid tumors.</p>

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Deciphering antigen-specific T cell navigation tactics and cancer immune evasion in co-cultures

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月31日

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  • Xinyue Li,
  • Taoli Jin,
  • Lisha Wang,
  • Senbin Wu,
  • Yerong Liu,
  • Ming Li,
  • Weijing Han,
  • Xuefei Li

摘要

Insufficient infiltration of cytotoxic T cells into solid tumors remains a critical obstacle in cancer immunotherapy. Despite extensive efforts to comprehend the mechanisms governing this limited infiltration, few studies have focused on the evolution of T cell motility behavior after co-culture. In this study, we combined quantitative cell trajectory analysis, computational modeling, and bulk/single-cell RNA sequencing to systematically characterize the impact of cell interactions. We reveal that in a 2.5D co-culture system with multiple cancer-cell clusters, cancer-specific T cells exhibit increased directional persistence, which facilitates their efficient searching of cancer-cell clusters. Additionally, these T cells form prolonged interactions with cancer cells, which is the most crucial factor for their accumulation on cancer-cell clusters. Furthermore, post-interaction, a cancer-cell subpopulation displays immunosuppressive traits, reducing T cell attractant expression, and undergoing epithelial-to-mesenchymal transition. These findings offer valuable insights into improving immunotherapy efficacy and tackling T cell infiltration challenges in solid tumors.