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Theranostics 2021; 11(11):5365-5386. doi:10.7150/thno.58390 This issue Cite

Review

Turning cold tumors into hot tumors by improving T-cell infiltration

Yuan-Tong Liu¹, Zhi-Jun Sun^1,2✉

1. The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine, Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
2. Department of Oral Maxillofacial-Head Neck Oncology, School and Hospital of Stomatology, Wuhan University, 237 Luoyu Road, Wuhan 430079, China.

✉ Corresponding author: Zhi-Jun Sun, Department of Oral Maxillofacial-Head Neck Oncology, School and Hospital of Stomatology, Wuhan University, 237 Luoyu Road, Wuhan 430079, Hubei Province, China. E-mail: sunzjedu.cn; Tel: +86 27 8768 6336; Fax: +86 27 8787 3260. More

Abstract

Immunotherapy, represented by immune checkpoint inhibitors (ICIs), has greatly improved the clinical efficacy of malignant tumor therapy. ICI-mediated antitumor responses depend on the infiltration of T cells capable of recognizing and killing tumor cells. ICIs are not effective in "cold tumors", which are characterized by the lack of T-cell infiltration. To realize the full potential of immunotherapy and solve this obstacle, it is essential to understand the drivers of T-cell infiltration into tumors. We present a critical review of our understanding of the mechanisms underlying “cold tumors”, including impaired T-cell priming and deficient T-cell homing to tumor beds. “Hot tumors” with significant T-cell infiltration are associated with better ICI efficacy. In this review, we summarize multiple strategies that promote the transformation of "cold tumors" into “hot tumors” and discuss the mechanisms by which these strategies lead to increased T-cell infiltration. Finally, we discuss the application of nanomaterials to tumor immunotherapy and provide an outlook on the future of this emerging field. The combination of nanomedicines and immunotherapy enhances cross-presentation of tumor antigens and promotes T-cell priming and infiltration. A deeper understanding of these mechanisms opens new possibilities for the development of multiple T cell-based combination therapies to improve ICI effectiveness.

Keywords: cold tumor, immune checkpoint inhibitors, T-cell infiltration, T-cell priming, nanomedicine

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