Immune-associated plasma proteins in oral and oropharyngeal cancer patients

Supranee Buranapraditkun; Patnarin Mahattanasakul; Areeya Diloktaweewattana; Narumol Bhummaphan; Chutha Siriwattanakankul; Fardeela Bin-Alee; Napadon Tangjaturonrasme; Apiwat Mutirangura; Nakarin Kitkumthorn

doi:10.1016/j.heliyon.2022.e10753

Immune-associated plasma proteins in oral and oropharyngeal cancer patients

Heliyon. 2022 Sep 27;8(9):e10753. doi: 10.1016/j.heliyon.2022.e10753. eCollection 2022 Sep.

Authors

Affiliations

¹ Division of Allergy and Clinical Immunology, Department of Medicine, King Chulalongkorn Memorial Hospital, Faculty of Medicine, Chulalongkorn University, Thai Red Cross Society, Bangkok 10330, Thailand.
² Center of Excellence in Vaccine Research and Development (Chula Vaccine Research Center-Chula VRC), Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.
³ Thai Pediatric Gastroenterology, Hepatology and Immunology (TPGHAI) Research Unit, King Chulalongkorn Memorial Hospital, Faculty of Medicine, Chulalongkon University, The Thai Red Cross Society, Bangkok 10330, Thailand.
⁴ Department of Otolaryngology, Head and Neck Surgery, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand.
⁵ Department of Otolaryngology, Head and Neck Surgery, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.
⁶ Division of Dengue Hemorrhagic Fever Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
⁷ Siriraj Center of Research Excellence in Dengue and Emerging Pathogens, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
⁸ College of Public Health Sciences, Chulalongkorn University, Bangkok, 10330, Thailand.
⁹ Center of Excellence in Molecular Genetics of Cancer and Human Diseases, Department of Anatomy, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.
¹⁰ Faculty of Medicine, Princess of Naradhiwas University, Narathiwat 96000, Thailand.
¹¹ Department of Oral Biology, Faculty of Dentistry, Mahidol University, Bangkok 10400, Thailand.

Abstract

Background: Plasma protein patterns differ between cancer patients and healthy donors. This study aimed to examine the plasma levels of several cytokines and immunological checkpoint proteins between patients with oral and oropharyngeal cancer and healthy donors.

Materials and methods: Plasma samples from healthy donors, oral cancer patients, and oropharyngeal cancer patients were analyzed using the Human Th Cytokine Panel 13-plex (IL-2, 4, 5, 6, 9, 10, 13, 17A, 17F, 21, 22, IFN-γ, and TNF-α) and Human Immune Checkpoint Panel1 12-plex [sCD25 (IL-2Ra), 4-1BB, sCD27, B7.2 (CD86), Free Active TGF-β1, CTLA-4, PD-L1, PD-L2, PD-1, Tim-3, LAG-3, and Galectin-9]. The plasma 4-1BB levels were verified by Western blot method. In addition, the study of the receive operating curve (ROC) yielded the calculation of a number of diagnostically significant indicators.

Results: Significantly increased levels of IL-6, 4-1BB, PDL-1, PD-1, and CTLA-4 and decreased levels of IL-13 and sCD27 were observed in cancer patients compared with healthy donors. These levels were highly significant, particularly for cancer patients in stage IV. Validation by Western blot revealed that cancer patients had higher plasma levels of 4-1BB than healthy donors (p < 0.05), and ROC curve analysis revealed that plasma 4-1BB had the highest cancer detection capability. Intriguingly, plasma levels of 4-1BB were significantly positively correlated with PDL-1 and PD-1 levels (p < 0.0001).

Conclusion: This data provided descriptive knowledge of oral and oropharyngeal cancer immunity at a fundamental level. Additional research should concentrate on the significantly different factors, especially 4-1BB, PDL-1, and PD-1, which may contribute to the development of novel alternative diagnostic tools or therapies for patients with oral and oropharyngeal cancer.

Keywords: Cytokine; Immune checkpoint; Oral cancer; Oropharyngeal cancer; Plasma.