The Clinical Relevance of Immune Cells and CTC in HNSCC Patients

Head and neck squamous cell carcinomas (HNSCCs) are mainly caused by tobacco, alcohol consumption and betel nut chewing and the sixth most common cancer in the world. Despite significant advances in the treatment modalities involving surgery, radiotherapy, and concomitant chemoradiotherapy, the 5-year survival rate remained below 50% for the past 30 years. The worse prognosis of these cancers must certainly be linked to the fact that HNSCCs strongly influence the host immune system. During this process, mesenchymal tumor-like cells are highly mobile and enter quickly adjacent structure (intravasation), from where they travel through lymphatic and blood vessels as circulating tumor cells (CTC), which are single cells with malignant potential detected in the peripheral bloodstream and essential for establishing metastasis. Programmed death 1 (PD-1) and its ligand (PD-L1) play pivotal roles in regulating host immune responses. Substantial evidence has demonstrated that PD-L1 can deliver an inhibitory signal to PD-1 expressing T cells, leading to suppression of the immune response by inducing apoptosis, energy, unresponsiveness and functional exhaustion of T cells. However, the inhibitory effects of this pathway on the function of cytotoxic T lymphocytes, the main effector cells in HNSCC patients, are not well defined. In this study aims to solve two main problems: one is to improve and try to optimize current protocols of CTC isolations based on the investigator previous work, which is one of most challenging problems in CTC field to date; the other is to understand the status of immune system in HNSCC patients, especially focusing on PD-1-PD-L1 pathway and its expressions. After series basic experiments of immune cell analysis and conditional adjustment of CTC isolation protocols, the investigator are willing to isolate CTCs and immune cells at a single blood drawing at the same time. A prospective trial will be conducted to elucidate the roles of PD-1 expression lymphocytes and CTC numbers on the clinical outcomes of HNSCC patients.

Sex

All

Minimum age

20 Years

Inclusion Criteria:

1. Established head and neck squamous cell carcinoma.
2. Age \>=20 years old with clear consciousness, decided by free wills.

Ability to sign informed consent

Exclusion Criteria:

1. Patient's refusal
2. Poor compliance, cannot draw blood for CTCs isolation as time schedule or clinical treatment or follow-up
3. Difficult blood sampling
4. No more needs for CTCs evaluation, decided by clinicians.

Inability to comply with study and/or follow-up procedures.

• RESULTHsieh JC, Lin HC, Huang CY, Hsu HL, Wu TM, Lee CL, Chen MC, Wang HM, Tseng CP. Prognostic value of circulating tumor cells with podoplanin expression in patients with locally advanced or metastatic head and neck squamous cell carcinoma. Head Neck. 2015 Oct;37(10):1448-55. doi: 10.1002/hed.23779. Epub 2014 Jul 24. PMID 24844673
• DERIVEDChang PH, Wu MH, Liu SY, Wang HM, Huang WK, Liao CT, Yen TC, Ng SH, Chen JS, Lin YC, Lin HC, Hsieh JC. The Prognostic Roles of Pretreatment Circulating Tumor Cells, Circulating Cancer Stem-Like Cells, and Programmed Cell Death-1 Expression on Peripheral Lymphocytes in Patients with Initially Unresectable, Recurrent or Metastatic Head and Neck Cancer: An Exploratory Study of Three Biomarkers in One-time Blood Drawing. Cancers (Basel). 2019 Apr 15;11(4):540. doi: 10.3390/cancers11040540. PMID 30991692