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Cellular and Molecular Biology

Enhanced antitumour response of gold nanostar-mediated photothermal therapy in combination with immunotherapy in a mouse model of colon carcinoma

British Journal of Cancer volume 130, pages 406–416 (2024)Cite this article

Subjects

Abstract

Objectives

This study investigated the potential of combining PTT with dendritic cell (DC)-based immunotherapy and anti-PD-L1 immune checkpoint blockade (ICB) therapy against colorectal cancer and elucidated the underlying mechanisms.

Methods

The CT26 tumour-bearing mice were divided into seven treatment groups: control, atezolizumab (A), dendritic cells (DC), pAuNSs-mediated PTT (PTT), PTT combined with atezolizumab (PTT + A), PTT combined with dendritic cells (PTT + DC), and PTT combined with dendritic cells and atezolizumab (PTT + DC + A). Therapeutic efficacy was monitored.

Results

PTT upregulated most immune cell membrane receptor genes, including PD-L1, and downregulated genes associated with antigen presentation and T cell activation. Although the PTT + A and PTT + DC treatments showed partial tumour growth retardation, the combination of PTT with DCs and atezolizumab (PTT + DC + A) exhibited the most significant antitumour effect, with a complete remission rate of 50% and prolonged survival. On day 14, tumour samples from non-responsive mice revealed insufficient recruitment of T cells as the reason for uncured tumours. Notably, mice cured with PTT + DC and PTT + DC + A treatments showed no detectable lung nodules.

Conclusion

This study demonstrated that the combination of PTT with DC-based immunotherapy and atezolizumab effectively overcomes the non-sensitive nature of CT26 tumours. These findings highlight the potential of this combination approach for colorectal cancer treatment.

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Fig. 1: The physicochemical and biological characteristics of unlabeled and radiolabeled pAuNSs.
Fig. 2: The next generation sequence analysis (NGS) after PTT.
Fig. 3: The in vitro and in vivo properties of 111In-atezolizumab.
Fig. 4: The effectiveness of monotherapy and combination therapy.
Fig. 5: The immunological analyses of tumors and spleens in each group of mice.

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Data availability

All data generated and analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors acknowledge the technical supports provided by Imaging and Flow cytometry Core Facility of National Yang Ming Chiao Tung University (Taipei, Taiwan) and Laboratory Animal Center, Chang Gung Memorial Hospital (Linkou, Taiwan).

Funding

The authors thank the financial support from National Sciences and Technology Council, Taiwan (MOST 109-2314-B-010-066, MOST 111-2623-E-A49-004-NU, and NSTC 112-2623-E-A49-006-NU).

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Authors and Affiliations

  1. Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan

    Hsin-Hua Hsieh, Chuan-Lin Chen, Hui-Wen Chan, Kwan-Hwa Chi & Chun-Yi Wu

  2. Department of Radiation Therapy and Oncology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, 111, Taiwan

    Kwan-Hwa Chi

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Contributions

H-HH: writing—original draft, investigation, methodology, software, formal analysis, data curation, visualisation; C-LC: resources, funding acquisition, project administration; H-WC: investigation, methodology; K-HC: supervision; C-YW: writing—review and editing, funding acquisition, supervision, validation, conceptualisation.

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Correspondence to Chun-Yi Wu.

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Animal studies were approved by the Institutional Animal Care and Use Committee, National Yang Ming Chiao Tung University, Taipei, Taiwan (Nos. 1100429 and 1101009).

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Hsieh, HH., Chen, CL., Chan, HW. et al. Enhanced antitumour response of gold nanostar-mediated photothermal therapy in combination with immunotherapy in a mouse model of colon carcinoma. Br J Cancer 130, 406–416 (2024). https://doi.org/10.1038/s41416-023-02537-y

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