Abstract
Objectives To evaluate apoptotic levels of peripheral blood mononuclear cells (PBMCs) and apoptotic regulatory proteins (Bax and Bcl-2) in lymphocyte subsets of oral cancer (OC) patients and healthy controls (HC).Methodology The percentage of apoptotic cells and lymphocyte counts were measured in the first cohort using PBMCs obtained from 23 OC patients and 6 HC. In the second cohort, (OC, 33; HC, 13), the mean fluorescence intensity (MFI) of Bax and Bcl-2 in CD19+ B, CD4+ T, CD8+ T, and CD16+56+ natural killer (NK) cells was determined via flow cytometry.Results The percentage of apoptotic cells was higher in the PBMCs of OC patients than in HC patients, particularly in patients with stage IV cancer (p<0.05). However, lymphocyte counts were significantly lower in stage IV patients (p<0.05). NK CD19+ B and CD16+56+ cell counts were significantly lower in OC patients compared with HC patients (p<0.001 and p<0.01, respectively), but CD4+ T cells were interestingly significantly higher in OC patients (p<0.001). While Bax MFI was slightly higher, Bcl-2 MFI was significantly lower for all four lymphocyte subsets in OC samples, particularly in stage IV patients, when compared with HC. Consequently, Bax/Bcl-2 ratios showed an upward trend from HC to OC patients, particularly those in stage IV. We found similar trends in Bax and Bcl-2 MFI for tumor stage, tumor size, and lymph node involvement.Conclusions The increased lymphocyte apoptosis in stage IV OC patients may be related to higher Bax levels and lower Bcl-2 levels. The Bax/Bcl-2 ratio in lymphocytes may be useful to determine the prognosis of OC patients, and could be considered a mean for supportive treatment in the future.
Highlights
Oral cancer (OC) is a worldwide common type of malignancy.1 This cancer originates from the stratified squamous epithelium of the oral cavity and is called oral squamous cell carcinoma (OSCC).2 It is often diagnosed at advanced stages, entailing fatalities and low survival rates.3 During metastasis, OSCC patients experience weakness and fatigue, are susceptible to infection, and commonly present leukopenia.4-6 Low lymphocyte counts may lead to a decrease in immune system’s ability to inhibit cancer development, promoting tumor growth and worsening prognosis.7oral cancer (OC) has an immune-escape mechanism
B-cell lymphoma-2 (Bcl-2)-associated X (Bax)/Bcl-2 ratio in CD19+ B, CD8+ T, and CD16+56+ natural killer (NK) cells were slightly higher in OC samples than in healthy controls (HC) samples
Lymphocytes are an important type of immune cells that have been targeted for the treatment of OC22 for being capable of recognizing cancer antigen and destroying cancer cells
Summary
Oral cancer (OC) is a worldwide common type of malignancy. This cancer originates from the stratified squamous epithelium of the oral cavity and is called oral squamous cell carcinoma (OSCC). It is often diagnosed at advanced stages, entailing fatalities and low survival rates. During metastasis (stage IV), OSCC patients experience weakness and fatigue, are susceptible to infection, and commonly present leukopenia. Low lymphocyte counts (lymphopenia) may lead to a decrease in immune system’s ability to inhibit cancer development, promoting tumor growth and worsening prognosis.7OC has an immune-escape mechanism. Oral cancer (OC) is a worldwide common type of malignancy.1 This cancer originates from the stratified squamous epithelium of the oral cavity and is called oral squamous cell carcinoma (OSCC).. This cancer originates from the stratified squamous epithelium of the oral cavity and is called oral squamous cell carcinoma (OSCC).2 It is often diagnosed at advanced stages, entailing fatalities and low survival rates.. Malignant cells are associated with immune suppression, enabling cancer cells to evade the host’s immune surveillance.. The impaired function of the immune system might be directly associated with head and neck squamous cell carcinomas (HNSCC) growth and metastasis.. It has been reported that tumor cells can escape immune surveillance, inhibit immune function, and induce immunogenic cell death and lymphocyte apoptosis, changing lymphocyte homeostasis. Malignant cells are associated with immune suppression, enabling cancer cells to evade the host’s immune surveillance. The impaired function of the immune system might be directly associated with head and neck squamous cell carcinomas (HNSCC) growth and metastasis. It has been reported that tumor cells can escape immune surveillance, inhibit immune function, and induce immunogenic cell death and lymphocyte apoptosis, changing lymphocyte homeostasis.
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