Thermalization of Cold Tumor: A Comprehensive Treatment Path for the Transformation of Cold Tumor to Hot Tumor
DOI:
https://doi.org/10.61173/hn7a4330Keywords:
- cold tumor, hot tumor, thermalization of cold tumor, tumor microenvironment, immunotherapyAbstract
This article reviews the emerging comprehensive treatment strategies for the transformation of "cold tumor" to "hot tumor", aiming to overcome the limitations of immunotherapy in tumors with low response rates. "Hot tumors" usually have abundant immune cell infiltration and active immune microenvironment, while "cold tumors" respond poorly to immunotherapy due to less immune cell infiltration and strong inhibitory microenvironment. This article focuses on three TME remodeling strategies: Tesla Cell activates innate immunity through metabolic reprogramming (such as inhibition of LDH-A and neutralization of lactate); Near-infrared photoimmunotherapy (NIR- PIT) uses photosensitizers to induce immunogenic death and reverse the immunosuppressive microenvironment. Hyperthermia enhances the activity of immune cells by directly killing tumor cells with high temperature and releasing antigens. In addition, this article analyzes the potential of these strategies in combination with immune checkpoint inhibitors, adoptive cell therapy and tumor vaccines, and compares their intrinsic/exogenous characteristics, safety and clinical transformation prospects. The "hyperthermia" of cold tumors provides a new direction for immunotherapy, which is expected to significantly improve the efficacy of refractory tumors.
References
[1] G. Cao, “The epidemiological characteristics, prevention and control status, and future response strategies of cancer in China,” J. Naval Med. Univ., vol. 46, no. 03, pp. 279–290, 2025.
[2] Y. Chen and J. Ding, “Opportunities and challenges of tumor immunotherapy,” J. Clin. Med. Ther., vol. 22, no. 01, pp. 1–6+25, 2024.
[3] R. Guo, Q. Tan, and J. Ma, “Remodeling the tumor microenvironment to improve the efficacy of immunotherapy,” Chin. Front. Med. Sci. (Electron. Ed.), vol. 15, no. 10, pp. 101– 110, 2023.
[4] X. Yuan, Y. Xiao, and D. Yu, “Turn cold tumors hot by reprogramming the tumor microenvironment,” Nat. Biotechnol., vol. 43, pp. 466–470, 2025.
[5] Y. Liu, W. Han, and J. Jiang, “Tumor microenvironment ‘cold-hot transition’: Cell battery (Tesla Cell),” Chin. J. Cancer Biother., vol. 31, no. 12, pp. 1167–1177, 2024.
[6] Y. Shi and J. Feng, “Research progress on nearinfrared photoimmunotherapy strategies targeting the tumor microenvironment,” China Prescriptions, vol. 23, no. 01, pp. 104–107, 2025.
[7] A. D. Garg et al., “Immunogenic cell death in cancer therapy: concepts and clinical implications,” Trends Immunol., vol. 38, no. 4, pp. 261–275, 2017.
[8] L. Galluzzi et al., “Consensus guidelines for the definition, detection, and interpretation of immunogenic cell death,” Oncoimmunology, vol. 9, no. 1, p. e1703446, 2020.
[9] M. Mitsunaga et al., “CD44-targeted near-infrared photoimmunotherapy for malignant pleural mesothelioma,” J. Control. Release, vol. 330, pp. 1069–1078, 2021.
[10] T. Nagaya et al., “Near-infrared photoimmunotherapy targeting EGFR-expressing head and neck squamous cell carcinoma,” Mol. Cancer Ther., vol. 19, no. 10, pp. 2013–2021, 2020.
[11] N. Yang, B. Liu, S. Zhang et al., “Research progress on the impact of hyperthermia on tumor immunity and combination with immunotherapy,” J. Drug Eval., vol. 48, no. 01, pp. 250– 255, 2025.
[12] F. Han and N. Li, “The impact of concurrent thermoradiotherapy and chemotherapy on tumor markers and the expression of miR-21 and miR-130 in patients with advanced cervical cancer,” Clin. Med. Res. Pract., vol. 9, no. 20, pp. 59– 63, 2024.
[13] B. Wu, B. Zhang, B. Li et al., “Cold and hot tumors: from molecular mechanisms to targeted therapy,” Sig. Transduct. Target Ther., vol. 9, p. 274, 2024.
[14] N. Lyu, Y. N. Kong, X. X. Li et al., “Ablation reboosts the response in advanced hepatocellular carcinoma with stable or atypical response during PD-1 therapy: A proof-of-concept study,” Front. Oncol., vol. 10, p. 580241, 2020.
[15] M. Xu, Y. Hao, and Z. Song, “The post-immune checkpoint inhibitor era: Hopes and challenges of immunotherapy for lung cancer,” Oncol., vol. 44, no. 06, pp. 598–620, 2024.
[16] S. A. Rosenberg, N. P. Restifo, J. C. Yang, R. A. Morgan, and M. E. Dudley, “Adoptive cell transfer: a clinical path to effective cancer immunotherapy,” Nat. Rev. Cancer, vol. 8, no. 4, pp. 299–308, 2008.
[17] P. A. Ott et al., “An immunogenic personal neoantigen vaccine for patients with melanoma,” Nature, vol. 547, pp. 217– 221, 2017.
[18] H. Kobayashi et al., “Near-infrared photoimmunotherapy of cancer,” Acc. Chem. Res., vol. 52, no. 8, pp. 2332–2339, 2019.
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