Hypoxia-Targeted Immunotherapy with PD-1 Blockade in Head and Neck Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Cell Lines
2.2. Patients and Immunohistochemistry (IHC)
2.3. Cell Culture and Hypoxic Conditions
2.4. Synthetic Peptide
2.5. Flow Cytometry
2.6. In Vitro Induction of MTH1-Specific CD4+ T Cells
2.7. Antigen-Specific Responses by MTH1-Specific HTLs
2.8. Cytotoxicity Assay
2.9. Cell Cycle Assay
2.10. Statistical Analysis
3. Results
3.1. Immunogenic Changes in HNSCC Cell Lines under Hypoxic Condition
3.2. Viability and Proliferation of T Cells under Hypoxic Conditions
3.3. MTH1 Expression in Patients with HNSCC and HNSCC Cell Lines
3.4. Generation of MTH145–59 Reactive CD4+ T-Cell Lines with Cytotoxic Activity
3.5. MTH145–59-Reactive T Cells in Periphery Blood from Patients with HNSCC
3.6. Antitumor Activity of MTH145–59-Reactive CD4+ T Cells with PD-1 Blockade in Hypoxia
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Clinical Feature | MTH1 IHC Score | p Value | |
---|---|---|---|
Low | High | ||
Gender | |||
Female | 1 | 6 | 0.2187 |
Male | 22 | 26 | |
Age (years) | |||
<70 | 14 | 17 | 0.5678 |
≥70 | 9 | 15 | |
HPV status | |||
Negative | 11 | 19 | 0.3962 |
Positive | 12 | 13 | |
T classificaion | |||
T1–2 | 11 | 18 | 0.5371 |
T3–4 | 12 | 14 | |
N classification | |||
N0–1 | 16 | 20 | 0.5868 |
N2–3 | 7 | 12 | |
Stage | |||
I, II | 13 | 13 | 0.2441 |
III, IV | 10 | 19 |
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Share and Cite
Wakisaka, R.; Yamaki, H.; Kono, M.; Inoue, T.; Sato, R.; Komatsuda, H.; Ohara, K.; Kosaka, A.; Ohkuri, T.; Nagato, T.; et al. Hypoxia-Targeted Immunotherapy with PD-1 Blockade in Head and Neck Cancer. Cancers 2024, 16, 3013. https://doi.org/10.3390/cancers16173013
Wakisaka R, Yamaki H, Kono M, Inoue T, Sato R, Komatsuda H, Ohara K, Kosaka A, Ohkuri T, Nagato T, et al. Hypoxia-Targeted Immunotherapy with PD-1 Blockade in Head and Neck Cancer. Cancers. 2024; 16(17):3013. https://doi.org/10.3390/cancers16173013
Chicago/Turabian StyleWakisaka, Risa, Hidekiyo Yamaki, Michihisa Kono, Takahiro Inoue, Ryosuke Sato, Hiroki Komatsuda, Kenzo Ohara, Akemi Kosaka, Takayuki Ohkuri, Toshihiro Nagato, and et al. 2024. "Hypoxia-Targeted Immunotherapy with PD-1 Blockade in Head and Neck Cancer" Cancers 16, no. 17: 3013. https://doi.org/10.3390/cancers16173013