Cell surface markers for T and B lymphocytes activation and adhesion as putative prognostic biomarkers for head and neck squamous cell carcinoma

Andrade, Mariléia Cháves; Ferreira, Sebastião Rodrigo; Gonçalves, Luiz Gustavo Vieira; De-Paula, Alfredo Maurício Batista; Faria, Elaine Speziali de; Teixeira-Carvalho, Andréa; Martins‐Filho, Olindo Assis

doi:10.1016/j.humimm.2013.08.272

Cited by 8 publications

(4 citation statements)

References 27 publications

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“…Further, we only investigated the presence of tumor infiltrating immune cells in head and neck SCC, in order to recognize a basic distinction in immune association between oropharynx cancer associated with HPV (p16-sg) or not (p16-ns). However, several studies [17,[33][34][35][36] showed that it might be of importance to further explore the organization, activation status and gene signature of the infiltrating immune cells, their functionality and target specificity, as well as the expression of immune-activating and immune-suppressing genes in the tumor microenvironment in order to fully understand the role of the immune system in better treatment response for patients with HPV þ HNSCC.…”

Section: Discussionmentioning

confidence: 99%

Immune cell infiltration in head and neck squamous cell carcinoma and patient outcome: a retrospective study

et al. 2018

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Section: Discussionmentioning

confidence: 99%

Immune cell infiltration in head and neck squamous cell carcinoma and patient outcome: a retrospective study

et al. 2018

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“…It has been reported that the amount of B cells that contribute to the humoral immune response are lower in SCCHN patients than in healthy individuals [6][7][8]. Belka et al were among the rst to describe B cells as the most sensitive lymphocyte subpopulation towards radiation since they rapidly undergo radiationinduced apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Comparison of the Composition of Lymphocyte Subpopulations in Non-relapse and Relapse Patients With Squamous Cell Carcinoma of the Head and Neck Before, During Radiochemotherapy and in the Follow-up Period: a Multicenter Prospective Study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG)

Niu

Combs

Linge

et al. 2020

Preprint

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Background: Radiochemotherapy (RCT) has been shown to induce changes in immune cell homeostasis which might affect antitumor immune responses. In the present study, we aimed to compare the composition and kinetics of major lymphocyte subsets in the periphery of patients with non-locoregional recurrent (n=23) and locoregional recurrent (n=9) squamous cell carcinoma of the head and neck (SCCHN) upon primary RCT.Methods: EDTA-blood of non-locoregional recurrent SCCHN patients was collected before (t0), after application of 20 to 30 Gy (t1), in the follow-up period 3 (t2) and 6 months (t3) after RCT. In patients with locoregional recurrence blood samples were taken at t0, t1, t2 and at the time of recurrence (t5). EDTA-blood of age-related, healthy volunteers (n=22) served as a control (Ctrl). Major lymphocyte subpopulations were phenotyped by multiparameter flow cytometry.Results: Patients with non-recurrent SCCHN had significantly lower proportions of CD19+ B cells compared to healthy individuals before start of any therapy (t0) that dropped further until 3 months after RCT (t2), but reached initial levels 6 months after RCT (t3). The proportion of CD3+ T and CD3+/CD4+ T helper cells continuously decreased between t0 and t3, whereas that of CD8+ cytotoxic T cells and CD3+/CD56+ NK-like T cells (NKT) gradually increased in the same period of time in non-recurrent patients. The percentage of CD4+/CD25+/FoxP3+ regulatory T cells (Tregs) decreased directly after RCT, but increased above initial levels in the follow-up period 3 (t2) and 6 (t3) months after RCT. Patients with locoregional recurrence showed similar trends with respect to B, T cells and Tregs between t0 and t5. CD4+ T helper cells remained stably low between t0 and t5 in patients with locoregional recurrence compared to Ctrl. NKT/NK cell subsets (CD56+/CD69+, CD3-/CD56+, CD3-/CD94+, CD3-/NKG2D+, CD3-/NKp30+, CD3-/NKp46+) increased continuously up to 6 months after RCT (t0-t3) in patients without locoregional recurrence, whereas in patients with locoregional recurrence, these subsets remained stably low until time of recurrence (t5).Conclusion: Monitoring the kinetics of lymphocyte subpopulations especially activatory NK cells before and after RCT might provide a clue with respect to the development of an early locoregional recurrence in patients with SCCHN. However, studies with larger patient cohorts are needed.

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“…Decreased frequency of CD19 + B lymphocytes in the peripheral circulation of HNSCC patients is associated with an increase in percentage of activated CD19 + HLA-DR + B cells. 52 Because activated B cells are CD39 + /CD73 + , produce immunoinhibitory adenosine, and inhibit functions of activated T cells, 53 they are considered “regulatory B cells.” Their accumulation in the periphery and lymph nodes of patients with HNSCC downregulates immunoresponses. On the other hand, accumulations of other B-cell subsets (eg, CD20 + B cells) in lymph nodes of HNSCC patients have been associated with favorable outcomes.…”

Section: Addressing Immunosuppression In Head and Neck Cancermentioning

confidence: 99%

IRX-2 natural cytokine biologic for immunotherapy in patients with head and neck cancers

Wolf¹,

Moyer²,

Kaplan³

et al. 2018

OTT

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Head and neck squamous cell carcinoma (HNSCC) is an immunosuppressive malignancy characterized by tumor-driven immune-system abnormalities that contribute to disease progression. For patients with surgically resectable HNSCC, treatment is often curative surgery followed by irradiation or chemoradiation in high-risk settings to reduce the risk of recurrence. Poor survival and considerable morbidity of current treatments suggest the need for new therapeutic modalities that can improve outcomes. Defects in antitumor immunity of HNSCC patients include suppressed dendritic cell (DC) maturation, deficient antigen-presenting cell function, compromised natural killer (NK)-cell cytotoxicity, increased apoptosis of activated T lymphocytes, and impaired immune-cell migration to tumor sites. Strategies for relieving immunosuppression and restoring antitumor immune functions could benefit HNSCC patients. IRX-2 is a primary cell-derived biologic consisting of physiologic levels of T-helper type 1 cytokines produced by stimulating peripheral blood mononuclear cells of normal donors with phytohemagglutinin. The primary active components in IRX-2 are IL2, IL1β, IFNγ, and TNFα. In vitro, IRX-2 acts on multiple immune-system cell types, including DCs, T cells, and NK cells, to overcome tumor-mediated immunosuppression. In clinical settings, IRX-2 is administered as part of a 21-day neoadjuvant regimen, which includes additional pharmacologic agents (low-dose cyclophosphamide, indomethacin, and zinc) to promote anticancer immunoresponses. In a Phase IIA trial in 27 patients with surgically resectable, previously untreated HNSCC, neoadjuvant IRX-2 increased infiltration of T cells, B cells, and DCs into tumors and was associated with radiological reductions in tumor size. Event-free survival was 64% at 2 years, and overall 5-year survival was 65%. Follow-up and data analysis are under way in the multicenter, randomized, Phase IIB INSPIRE trial evaluating the IRX-2 regimen as a stand-alone therapy for activating the immune system to recognize and attack tumors.

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Cell surface markers for T and B lymphocytes activation and adhesion as putative prognostic biomarkers for head and neck squamous cell carcinoma

Cited by 8 publications

References 27 publications

Immune cell infiltration in head and neck squamous cell carcinoma and patient outcome: a retrospective study

Immune cell infiltration in head and neck squamous cell carcinoma and patient outcome: a retrospective study

IRX-2 natural cytokine biologic for immunotherapy in patients with head and neck cancers

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