Immunophenotyping of patients with oral squamous cell carcinoma in peripheral blood and associated tumor tissue
Martin Grimm1, Oliver Feyen2, Heiko Hofmann3
1Department of Oral and Maxillofacial Surgery, University Hospital Tübingen, Osianderstrasse 2-8, 72076, Tübingen, Germany. dr.dr.martingrimm@googlemail.com.
Abstract:
The immune system is important for elimination of cancer cells. Tumors including oral squamous cell carcinoma (OSCC) are capable of escaping detection by host immune cells through apoptotic depletion of tumor-infiltrating lymphocytes (TILs). Circulating peripheral blood lymphocytes (PBLs) and corresponding TILs of tumor specimen were evaluated before and after curative tumor resection (n = 30) compared with PBLs of controls (n = 87). PBLs were characterized for the total number of T cells (CD3(+)), T helper cells (Th, CD3(+)/CD4(+)), regulatory T cells (Treg, CD4(+)/CD25(+)/CD127(low)), cytotoxic T cells (Tc, CD3(+)/CD8(+)), activated T cells (CD3(+)/HLA-DR(+)), and natural killer (NK) cells (CD3(-)/CD16(+)/CD56(+)). In tumor tissue, the prevalence of CD3(+), CD4(+), and CD8(+) TILs was assessed using immunohistochemistry, whereas the incidence of apoptosis was assessed using terminal deoxynucleotidyl transferase deoxyuridinetriphosphate nick-end labeling (TUNEL) assay. In PBLs of pretreated OSCC patients, a highly significant decrease in total number of T cells (p = 0.0001), Th cells (p < 0.0001), Treg cells (p < 0.0001), Tc cells (p < 0.0001), and NK cells (p = 0.0037) were found compared with controls. Decreased PBLs of OSCC patients were correlated with decreased numbers of corresponding TILs, which were associated with increased detection of apoptosis in the tumor tissue. Compared with the controls, the total number of T cells remained unchanged after surgery but the total number of NK cells significantly increased. Standardized immunophenotyping of OSCC may help to identify patients likely to benefit from cancer immunotherapy strategies and/or chemoradiation. Finally, future attempts to enhance an effective tumor-reactive immune response by immunotherapy or vaccination should be made by promoting tumor-specific Th and/or Tc cell/NK cell responses.
Insights
Oral squamous cell carcinoma (OSCC) patients show decreased immune cells, correlating with tumor apoptosis. Surgery partially restores immune cell counts, suggesting immunotherapy targets for OSCC treatment.
Area of Science:
- Immunology
- Oncology
- Cell Biology
Background:
- The immune system plays a crucial role in eliminating cancer cells.
- Oral squamous cell carcinoma (OSCC) can evade immune detection through lymphocyte apoptosis.
- Tumor-infiltrating lymphocytes (TILs) and peripheral blood lymphocytes (PBLs) are key indicators of immune status in cancer.
Purpose of the Study:
- To evaluate immune cell profiles in OSCC patients before and after tumor resection.
- To correlate changes in PBLs and TILs with tumor apoptosis.
- To identify potential biomarkers for immunotherapy in OSCC.
Main Methods:
- Immunophenotyping of PBLs (T cells, Th, Treg, Tc, activated T cells, NK cells) and TILs.
- Assessment of apoptosis in tumor tissue using TUNEL assay.
- Comparison of immune cell counts in OSCC patients (n=30) and healthy controls (n=87).
Main Results:
- Pre-treatment OSCC patients exhibited significantly lower levels of T cells, Th, Treg, Tc, and NK cells compared to controls.
- Reduced PBL counts correlated with decreased TILs and increased tumor apoptosis.
- Post-surgery, T cell counts normalized, while NK cell counts significantly increased.
Conclusions:
- OSCC is associated with profound immune cell depletion, linked to tumor-induced apoptosis.
- Immunophenotyping can identify OSCC patients who may benefit from immunotherapy or chemoradiation.
- Enhancing tumor-specific T helper, cytotoxic T, and NK cell responses is crucial for effective cancer immunotherapy and vaccination strategies.


