Cytokine and Chemokine Signals of T-Cell Exclusion in Tumors

• Main Authors: Yu Zhang, Xin-yuan Guan, Peng Jiang
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2020-12-01
• Series: Frontiers in Immunology
• Subjects: T-cell exclusion; cell therapy; immunotherapy; cytokine; chemokine
• Online Access: https://www.frontiersin.org/articles/10.3389/fimmu.2020.594609/full

The success of cancer immunotherapy in solid tumors depends on a sufficient distribution of effector T cells into malignant lesions. However, immune-cold tumors utilize many T-cell exclusion mechanisms to resist immunotherapy. T cells have to go through three steps to fight against tumors: trafficking to the tumor core, surviving and expanding, and maintaining the memory phenotype for long-lasting responses. Cytokines and chemokines play critical roles in modulating the recruitment of T cells and the overall cellular compositions of the tumor microenvironment. Manipulating the cytokine or chemokine environment has brought success in preclinical models and early-stage clinical trials. However, depending on the immune context, the same cytokine or chemokine signals may exhibit either antitumor or protumor activities and induce unwanted side effects. Therefore, a comprehensive understanding of the cytokine and chemokine signals is the premise of overcoming T-cell exclusion for effective and innovative anti-cancer therapies.