Theranostics 2020; 10(4):1814-1832. doi:10.7150/thno.38515

Research Paper

Neutrophil infiltration and whole-cell vaccine elicited by N-dihydrogalactochitosan combined with NIR phototherapy to enhance antitumor immune response and T cell immune memory

Shuhong Qi1,2*, Lisen Lu1,2*, Feifan Zhou3, Yuzhou Chen1,2, Mengli Xu1,2, Lu Chen1,2, Xiang Yu1,2, Wei R. Chen3✉, Zhihong Zhang1,2✉

1. Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics-Huazhong University of Science and Technology, Wuhan, Hubei 430074, China
2. MoE Key Laboratory for Biomedical Photonics, Collaborative Innovation Center for Biomedical Engineering, School of Engineering Sciences, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China
3. Biophotonics Research Laboratory, Center for Interdisciplinary Biomedical Education and Research, College of Mathematics and Science, University of Central Oklahoma, Edmond, Oklahoma 73034, United States
* These authors contributed equally to this work

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Citation:
Qi S, Lu L, Zhou F, Chen Y, Xu M, Chen L, Yu X, Chen WR, Zhang Z. Neutrophil infiltration and whole-cell vaccine elicited by N-dihydrogalactochitosan combined with NIR phototherapy to enhance antitumor immune response and T cell immune memory. Theranostics 2020; 10(4):1814-1832. doi:10.7150/thno.38515. Available from http://www.thno.org/v10p1814.htm

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Abstract

Melanoma is one of the deadliest malignancies with a high risk of relapse and metastasis. Long-term, tumor-specific, and systemic immunity induced by local intervention is ideal for personalized cancer therapy. Laser immunotherapy (LIT), a combination of local irradiation of laser and local administration of an immunostimulant, was developed to achieve such an immunity. Although LIT showed promising efficacy on tumors, its immunological mechanism is still not understood, especially its spatio-temporal dynamics.

Methods: In this study, we investigated LIT-induced immunological responses using a 980-nm laser and a novel immunostimulant, N-dihydrogalactochitosan (GC). Then we followed the functions of key immune cells spatially and temporally using intravital imaging and immunological assays.

Results: Immediately after LIT, GC induced a rapid infiltration of neutrophils which ingested most GC in tumors. The cytokines released to the serum peaked at 12 h after LIT. Laser irradiations produced photothermal effects to ablate the tumor, release damage-associated molecular patterns, and generate whole-cell tumor vaccines. LIT-treated tumor-bearing mice efficiently resisted the rechallenged tumor and prevented lung metastasis. Intravital imaging of tumor at rechallenging sites in LIT-treated mice revealed that the infiltration of tumor-infiltrating lymphocytes (TILs) increased with highly active motility. Half of TILs with arrest and confined movements indicated that they had long-time interactions with tumor cells. Furthermore, LIT has synergistic effect with checkpoint blockade to improve antitumor efficacy.

Conclusion: Our research revealed the important role of LIT-induced neutrophil infiltration on the in situ whole-cell vaccine-elicited antitumor immune response and long-term T cell immune memory.

Keywords: laser immunotherapy, intravital imaging, whole-cell vaccine, immune memory