Immunological Strategies for Transforming ‘Cold’ Tumors into ‘Hot’ Tumors: Mechanistic Challenges and Future Perspectives

¹ School of Pharmacy, Nantong University, 226019 No. 9 Seyuan Road, Nantong, Jiangsu, China
² International Business School, Shaanxi Normal University, 710100, Chang’an District, Xi’an, Shaanxi, China
³ International Education College, Xinyang Normal University, 464000 No. 237 Nanhu Road, Shihe District, Xinyang, Henan, China

^* Corresponding author: This email address is being protected from spambots. You need JavaScript enabled to view it.

Abstract

Tumor immunotherapy has achieved impressive results on different kinds of cancer, but there are always some ‘cold tumors’ which reduce its best results. It’s mainly due to tumor cell antigen presentation deficiency as well as many other biological barriers, leading to the lack of T cell infiltration and an immunosuppressive microenvironment. This review has the task of looking into strategies for restarting the anti-tumor immune cycle so as to bring about a “cold” turning into a “warm” tumor transformation. This review mainly uses ways such as inducing ICD (immunogenic cell death) through radiotherapy, chemotherapy, or oncolytic viruses, so that tumor antigens can be released, and related innate immune pathways can be activated, such as cGAMP synthase (cGAS) and stimulator of interferon (STING), to make naive T cells react. Next up was to use combined modalities towards inhibiting cells and anti-angiogenic modalities to try to have more T cells infiltrate as well as change the immunosuppressive environment. Next, this review will use immune checkpoint inhibitors (ICIs) to wake asleep infiltrating T cells so they can do their job and have lasting anti-tumor effects.