Regulatory T cells and M2-polarized tumour-associated macrophages are associated with the oncogenesis and progression of oral squamous cell carcinoma

Kouketsu, Atsumu; Sato, Iwao; Oikawa, Masahiro; Shimizu, Yoshinaka; Saito, Hiroki; Tashiro, Kazuki; Yamashita, Yuichi; Takahashi, Tsuneo; Kumamoto, Hiroyuki

doi:10.1016/j.ijom.2019.04.004

Cited by 63 publications

(66 citation statements)

References 25 publications

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“…16,17,28,29 Information on possible sex-related differences in the number of Treg cells in the microenvironment of OSCC is scarce. 27 Kouketsu et al, 27 in a study on OSCC diagnosed in individuals aged 27 to 93 years, did not observe significant differences in the number of FoxP3+ lymphocytes in the microenvironment of lesions associated with patient sex. Similar results were obtained for OTSCC in the present study, both for young and older individuals (p > 0.05).…”

Section: Discussionmentioning

confidence: 94%

“…Kouketsu et al 27 assessed 82 cases of OSCC and did not observe any significant differences in the number of FoxP3+ lymphocytes in the tumor stroma when comparing age groups (27 to 93 years). Likewise, Ryu et al 26 analyzed 552 head and neck SCCs (HNSCCs), including cases of OTSCC, and did not observe significant differences in the number of FoxP3+ lymphocytes in the microenvironment of lesions in young individuals (≤ 45 years) and in those aged over 45 years.…”

Section: Discussionmentioning

confidence: 97%

“…There is a paucity of information on qualitative and/or quantitative age-related differences in cells of the immune system in the microenvironment of OSCC. 25,26,27 Accordingly, this study aimed to determine the number of Treg cells in the microenvironment of OTSCC in young and older individuals and to correlate the findings with clinicopathological parameters. The main hypothesis was that the number of Treg cells would be higher in OTSCC in older patients than in young ones.…”

Section: Discussionmentioning

confidence: 99%

“…26 Studies on the participation of Treg cells in the development and progression of OSCC have shown contradictory results. A larger number of these cell types in the microenvironment of OSCC have been associated with more advanced stages and worse prognosis 16,17,27,28 or with initial stages and higher survival rates. 18,29 The reasons for these discrepancies remain unclear, but the findings of the present study suggest that patient age could be an important confounding factor.…”

Section: Discussionmentioning

confidence: 99%

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FoxP3+ regulatory T cells in oral tongue squamous cell carcinoma in young and older patients

et al. 2020

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FoxP3+ regulatory T cells in oral tongue squamous cell carcinoma in young and older patients Abstract: Regulatory T (Treg) cells can suppress antitumor immune response, but little is known about possible age-related differences in the number of these cells in the microenvironment of oral tongue squamous cell carcinoma (OTSCC). The aim of this study was to determine the number of FoxP3+ Treg cells in the microenvironment of OTSCC in young (≤ 45 years) and older (≥ 60 years) patients, and to correlate the findings with clinicopathological parameters (sex, tumor size/extent, regional lymph node metastasis, clinical staging, and histopathological grade of malignancy). Forty-eight OTSCCs (24 diagnosed in young patients and 24 diagnosed in older patients) were selected. Lymphocytes exhibiting nuclear immunopositivity for FoxP3 were quantified at the tumor invasive front and the results were analyzed statistically using the non-parametric Mann-Whitney test. FoxP3+ lymphocytes were observed in all cases assessed. The number of FoxP3+ lymphocytes in OTSCC tended to be higher in older patients (p = 0.055). Analysis of OTSCC in males and in early clinical stages revealed a higher number of Treg cells in older patients than in young ones (p < 0.05). In older patients, the number of Treg cells tended to be higher in smaller tumors (p = 0.079). Tumors with intense inflammatory infiltrate exhibited a larger number of Treg cells, both in young (p = 0.099) and older patients (p = 0.005). The results suggest a greater participation of Treg cells in immunoinflammatory responses in the microenvironment of OTSCC in older patients, particularly in males and in early stages.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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FoxP3+ regulatory T cells in oral tongue squamous cell carcinoma in young and older patients

et al. 2020

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“…It has been described repeatedly that frequencies of T reg are elevated in the tumor environment reflecting an immunosuppressive micromilieu [19,43]. As a result of the fragile immune system in elderly, tumor-induced immune suppression may be less pronounced in aged patients.…”

Section: Expression Of Chemokine Receptor Ccr7mentioning

confidence: 99%

Age-related changes in T lymphocytes of patients with head and neck squamous cell carcinoma

et al. 2020

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Introduction: The number of aging cancer patients has increased continuously and will do so further in the future. The immune system of elderly people experiences critical changes over the time. Therefore, tumor-induced changes in the immune system are believed to differ in young and elderly cancer patients as well. Methods: The effect of aging on the immune system was measured in peripheral blood lymphocytes (PBL) of healthy volunteers (n = 48, 21-84 yrs.) divided into three different age groups. Seventy years was set as a cutoff for defining subjects as elderly. Results were compared to two groups of adult cancer patients, which donated PBL and tumor infiltrating lymphocytes (TIL): young cancer patients (40-69 yrs.; blood: n = 13; TIL: n = 17) and elderly cancer patients (70-90 yrs.; blood: n = 20; TIL: n = 15) with head and neck squamous cell carcinoma (HNSCC). Frequencies and phenotypes of CD4 + and CD8 + T cells as well as regulatory T cells (T reg) were assessed by flow cytometry. Results: We observed lower frequencies of CD8 + cytotoxic T cells during aging in both groups. Frequencies of tumor infiltrating regulatory T cells were significantly higher than in the peripheral blood but showed a significant decline in older tumor patients. With increasing age, expression of immunosuppressive CD73 and CCR7 was lower and expression of PD1 elevated on peripheral T cells in healthy volunteers and tumor patients. Conclusion: Immunosenescence takes place in healthy donors and cancer patients. Our results suggest that in elderly tumor patients, the immune system is impaired and the tumor-induced immune escape is less pronounced. The increased expression of PD1 implies the potential for effective immunotherapies in elderly, as treatment with checkpoint inhibitors could be more beneficial for elderly HNSCC patients.

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Tumor immune microenvironment in therapy‐naive esophageal adenocarcinoma could predict the nodal status

et al. 2022

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Background: Currently, preoperative staging of esophageal adenocarcinoma (EAC) has modest reliability and accuracy for pT and pN stages prediction, which heavily affects overall survival. The interplay among immune checkpoints, oncogenes, and intratumoral and peritumoral immune infiltrating cells could be used to predict loco-regional metastatic disease in early EAC. Methods:We prospectively evaluated immune markers expression and oncogenes status as well as intratumoral and peritumoral immune infiltrating cells populations in esophageal mucosa samples obtained from neoadjuvant therapynaïve patients who had esophagectomy for EAC.Results: Vascular invasion and high infiltration of lamina propria mononuclear cells resulted associated with nodal metastasis. Low infiltration of activated CD8 + CD28 + T cells was observed in both intratumoral and peritumoral mucosa of patients with nodal metastasis. Low levels of CD69, MYD88, and TLR4 transcripts were detected in the intratumoral specimen of patients with lymph node involvement. Receiver operating characteristic curve analysis showed good accuracy for detecting nodal metastasis for all the markers tested. Significant lower infiltration of CD8 T cells and M1 macrophages and a lower expression of CD8A, CD8B, and TBX21 were found also in Esophageal Adenocarcinoma TCGA pan-Cancer Atlas in the normal tissue of patients with nodal metastasis. Conclusions:Our data suggest that immune surveillance failure is the main driver of nodal metastasis onset. Moreover, nodal metastasis containment also involves the immune microenvironment of the peritumoral healthy tissue.

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Regulatory T cells and M2-polarized tumour-associated macrophages are associated with the oncogenesis and progression of oral squamous cell carcinoma

Cited by 63 publications

References 25 publications

FoxP3+ regulatory T cells in oral tongue squamous cell carcinoma in young and older patients

FoxP3+ regulatory T cells in oral tongue squamous cell carcinoma in young and older patients

Age-related changes in T lymphocytes of patients with head and neck squamous cell carcinoma

Tumor immune microenvironment in therapy‐naive esophageal adenocarcinoma could predict the nodal status

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