CD4CD8double-positive T cells in immune disorders and cancer: Prospects and hurdles in immunotherapy.

in Autoimmunity reviews by Md Rakibul Alam, Amos Olalekan Akinyemi, Jianlin Wang, Mithu Howlader, Mohammad Esfini Farahani, Maria Nur, Min Zhang, Lixiang Gu, Zhiguo Li

TLDR

  • DP T cells, a subset of T cells, are present in various species and play a role in immune disorders, inflammation, and cancer. Their high prevalence in advanced cancers and distinct cytokine profile make them a potential tool for immunotherapy.
  • Future research will aim to further understand DP T cell development and their therapeutic potential in various disease contexts.

Abstract

CD4and CD8T cells play critical roles in both innate and adaptive immune responses, managing and modulating cellular immunity during immune diseases and cancer. Their well-established functions have led to significant clinical benefits. CD4CD8double-positive (DP) T cells, a subset of the T cell population, have been identified in the blood and peripheral lymphoid tissues across various species. They have gained interest due to their involvement in immune disorders, inflammation, and cancer. Although mature DP T cells are present in healthy individuals and contribute to disease contexts, their molecular characteristics and pathophysiological roles remain debated. Notably, the number of DP T cells in the blood is higher in older adults compared to younger individuals, and these cells can stimulate inflammation and viral infections through increased secretion of interleukin (IL)-10, interferon gamma (IFN-γ), and transforming growth factor beta (TGF-β). In cancer, DP T cells have been observed to infiltrate cutaneous T cell lymphomas and are found in greater numbers in nodular lymphocyte predominant Hodgkin lymphoma, melanoma, hepatocellular carcinoma, and breast cancer. The higher prevalence of DP T cells in advanced cancers, coupled with their strong lytic activity and distinct cytokine profile, suggests that these cells may play a crucial role in modulating immune responses to cancer. This insight offers a potential new approach for enhancing the identification and selection of antigen-reactive T cells in immune-based treatments. This review provides a comprehensive overview of the origin, distribution, transcriptional regulation during developmental stages, and functions of DP T cells. A deeper understanding of the diversity and roles of DP T cells may pave the way for their development as a promising tool for immunotherapy in the management of immune disorders and metastatic cancers.

Overview

  • The study focuses on CD4/CD8 double-positive (DP) T cells, a subset of T cells with potential roles in immune disorders, inflammation, and cancer.
  • The researchers examine the molecular characteristics and pathophysiological roles of DP T cells, exploring their distribution, transcriptional regulation, and functions.
  • The study aims to improve understanding of DP T cells to potentially develop them as a tool for immunotherapy in immune disorders and metastatic cancers.

Comparative Analysis & Findings

  • DP T cells are present in blood and peripheral lymphoid tissues across various species and are more abundant in older adults compared to younger individuals.
  • DP T cells in cancer contexts, such as cutaneous T cell lymphoma, nodular lymphocyte predominant Hodgkin lymphoma, melanoma, hepatocellular carcinoma, and breast cancer, exhibit increased secretion of IL-10, IFN-γ, and TGF-β.
  • The prevalence of DP T cells is higher in advanced cancers, suggesting a role in modulating immune responses to cancer, and their strong lytic activity and distinct cytokine profile may be useful in immunotherapy.

Implications and Future Directions

  • Understanding the diversity and roles of DP T cells may lead to the development of a new approach for enhancing the identification and selection of antigen-reactive T cells in immune-based treatments.
  • Future research should address the limitations of the study, such as the need for a more comprehensive understanding of DP T cell development and the potential application of DP T cells in immunotherapy.
  • Building on the study's findings, future research directions may focus on exploring the therapeutic potential of DP T cells in various disease contexts and developing novel approaches for their clinical application.
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