Igniting Hope for Tumor Immunotherapy: Promoting the “Hot and Cold” Tumor Transition

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Abstract
The discovery of immune checkpoint inhibitors (ICIs) has ushered a new era for immunotherapy against malignant tumors through the killing effects of cytotoxic T lymphocytes in the tumor microenvironment (TME), resulting in long-lasting tumor suppression and regression. Nevertheless, given that ICIs are highly dependent on T cells in the TME and that most tumors lack T-cell infiltration, promoting the conversion of such immunosuppressive “cold” tumors to “hot” tumors is currently a key challenge in tumor immunotherapy. Herein, we systematically outlined the mechanisms underlying the formation of the immunosuppressive TME in cold tumors, including the role of immunosuppressive cells, impaired antigen presentation, transforming growth factor-β, STAT3 signaling, adenosine, and interferon-γ signaling. Moreover, therapeutic strategies for promoting cold tumors to hot tumors with adequate T-cell infiltration were also discussed. Finally, the prospects of therapeutic tools such as oncolytic viruses, nanoparticles, and photothermal therapy in restoring immune activity in cold tumors were thoroughly reviewed.
Funding Information
  • the Graduate Research- Innovation Project in Jiangsu province (SJCX22_1816)
  • The Social Development Project of Yangzhou, Jiangsu Province (No. YZ2021075)
  • the Graduate Research and Practice innovation Plan of Graduate Education Innovation Project in Jiangsu Province (N0. SJCX211644)
  • The Academic Science and Technology Innovation Fund for College Students (No. x20180714)
  • The Social Development-Health Care Project of Yangzhou, Jiangsu Province (No. YZ2018087)
  • High-level talent “six one projects” top talent scientific research project of Jiangsu Province (No. LGY2019034)
  • the Training Project of Key Talents of Youth Medicine in Jiangsu province, China (No. QNRC2016330)
  • The Key disease standardization diagnosis and treatment project in Jiangsu province (N0.BE2015664)
  • Social development project of key R & D plan of Jiangsu Provincial Department of science and technology (BE2022773)

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