Blood Of Head And Neck Squamous Cell Carcinoma Patients Research Articles

Application value of folate receptor-positive circulating tumor cells in the diagnosis of head and neck squamous cell carcinoma

A total of 82 patients and healthy subjects in the First Affiliated Hospital of Sun Yat-sen University from March to August 2023 were recruited. The cohort consisted of 43 patients with head and neck squamous cell carcinoma (HNSCC) and 39 non-cancer patients or healthy subjects. There were 63 males and 19 females, with a median age of 62 (46, 67) years. The levels of folate receptor-positive circulating tumor cells (FR+CTCs) in the blood of HNSCC patients and non-cancer/healthy subjects were 12.4 (8.5, 17.8) floate unit (FU)/3 ml and 5.0 (3.8, 6.6) FU/3 ml, respectively, with a statistically significant difference (P<0.001). The area under the receiver operating characteristic (ROC) curve for FR+CTCs levels was 0.937 (95%CI: 0.888-0.986, P<0.001), with a cut-off value of 7.4 FU/3 ml determined by the maximum Youden index. At this cut-off value, the sensitivity and specificity of FR+CTCs for diagnosing HNSCC were 90.70% and 89.74%, respectively. The current study suggests that FR+CTCs could be used as a liquid biopsy marker for the screening and diagnosis of HNSCC.

Exosomen: potenzielle Flüssigbiopsie bei Kopf-Hals-Karzinomen

Due to late diagnosis and poor treatment response, advanced head and neck squamous cell carcinoma (HNSCC) belongs to the tumor diseases with highest mortality worldwide. Although many biomarkers have been investigated over the past years, none have yet become established in clinical practice. There is thus an urgent need to introduce noninvasive liquid biopsies that not only give information about cancer activity but also enable early conclusions regarding treatment response. This underlines the biological importance of exosomes from the blood of HNSCC patients. Isolation of exosomes from cell line supernatants and human plasma can easily be performed by size-exclusion chromatography. Thus, protein content, expression patterns, and immunomodulatory effects on immune cells can be evaluated. Further separation of exosomes by cell of origin enables more detailed examination of tumor-derived exosomes (TEX) and exosomes from immune cells. The etiology of the disease, e.g., human papillomavirus (HPV) status, disease activity (active vs. no evident disease), and response to immunotherapies can be detected by exosomal protein expression and immunosuppressive effects of exosomes on different immune cell subtypes. In conclusion, the presented studies can make an essential contribution to the establishment of exosomes as liquid biopsies for head and neck cancer diagnosis and treatment monitoring.

EGFR inhibitors augment antitumour helper T-cell responses of HER family-specific immunotherapy

Background:Head and neck squamous cell carcinoma (HNSCC) is a major cause of cancer-related morbidity and mortality worldwide. Epidermal growth factor receptor (EGFR)-targeted therapy is an attractive strategy alternative to conventional cancer treatments for HNSCC, but its efficacy remains controversial. T-cell-based immunotherapy has been proposed as a novel therapeutic approach to improve the clinical outcome for HNSCC. In this study, we report human epidermal receptor (HER) family epitopes that induced CD4 T-cell responses to HNSCC. The results provide support for a novel strategy to treat HNSCC by combining EGFR-targeted therapy with T-cell-based immunotherapy.Methods:We evaluated the capacity of predicted CD4 T-cell peptide epitopes from EGFR to induce antitumour immune responses in vitro. In addition, EGFR inhibitors were evaluated for their ability to augment tumour MHC class II expression in HNSCC cell lines and subsequently increase T-cell recognition.Results:Among several predicted peptide epitopes, EGFR875–889 elicited CD4 T-cell responses that were restricted by HLA-DR4, DR15, or DR53 molecules, indicating that the peptide functions as a promiscuous T-cell epitope. The peptide-reactive T cells responded to autologous dendritic cells loaded with EGFR-expressing tumour cell lysates, indicating that these epitopes are naturally processed. In addition, the CD4 T cells were capable of directly recognising and killing HNSCC cells expressing EGFR and the appropriate HLA class II molecule. T cells reactive with the EGFR875–889 epitope could be detected in the blood of HNSCC patients. EGFR875–889-reactive CD4 T cells were also able to recognise several peptide analogues derived from homologous regions of EGFR family members, HER-2, HER-3 and c-MET. Finally, we examined the effects of EGFR tyrosine kinase inhibition or EGFR-blocking antibodies on CD4 T-cell tumour reactivity. Treatment of tumour cells with the EGFR inhibitors enhanced tumour recognition by EGFR875–889-reactive T cells presumably due to the upregulation of HLA-DR expression in the HNSCC cells.Conclusion:We identified novel CD4 T-cell EGFR epitopes and amongst these, EGFR875–889 functions as a promiscuous helper T-cell epitope that can elicit effective antitumour T-cell responses against tumours expressing HER family members and c-MET. These observations should facilitate the translation of T-cell-based immunotherapy into the clinic for the treatment of HNSCC and provide a rational basis for EGFR inhibition, immune-targeted combination therapy.