Immune Suppression in Head and Neck Cancers: A Review

Duray, Annaëlle; Demoulin, Stéphanie; Hubert, Pascale; Delvenne, Philippe; Saussez, Sven

doi:10.1155/2010/701657

Cited by 155 publications

(151 citation statements)

References 170 publications

(144 reference statements)

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“…14 In addition, decreased expression of NKG2D receptors has also been shown to impair NK cell function in HNSCC patients. 15,16 Indeed, similar effects have been demonstrated in regards to other malignancies, such as colorectal cancer, prostate cancer, neuroblastoma, and several types of leukemia. 11,[17][18][19] Interestingly, we demonstrated that sMICA and transforming growth factor b 1 (TGFb 1 ) compromise the function of activated donor NK cells applied as an immunotherapeutic approach in children with neuroblastoma after haploidentical stem cell transplantation (HSCT).…”

Section: Introductionmentioning

confidence: 59%

Increased sMICA and TGFβ ₁ levels in HNSCC patients impair NKG2D-dependent functionality of activated NK cells

et al. 2015

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Abbreviations: ADCC, antigen-dependent cellular cytotoxicity; HNSCC, head-and-neck squamous cell carcinoma; HSCT, haploidentical stem cell transplantation; KIR, killer cell immunoglobulin-like receptor; NCR, natural cytotoxicity receptor; NK, natural killer; NKG2D, natural-killer group 2, member D; vitsMICA/NKG2DL, soluble major histocompatibility complex Class I chain-related peptide A; TGFb1, transforming growth factor beta 1; TIEM, tumor immune escape mechanismDisseminated head-and-neck squamous cell carcinoma (HNSCC) escapes immune surveillance and thus frequently manifests as fatal disease. Here, we report on the distribution of distinct immune cell subpopulations, natural killer (NK) cell cytotoxicity and tumor immune escape mechanisms (TIEMs) in 55 HNSCC patients, either at initial diagnosis or present with tumor relapse. Compared to healthy controls, the regulatory NK cells and the ratio of pro/antiinflammatory cytokines were decreased in HNSCC patients, while soluble major histocompatibility complex Class I chain-related peptide A (sMICA) and transforming growth factor b 1 (TGFb 1 ) plasma levels were markedly elevated. Increased sMICA and TGFb 1 concentrations correlated with tumor progression and staging characteristics in 7 follow-up HNSCC patients, with significantly elevated levels of both soluble factors from the time of initial diagnosis to that of relapse. Patient plasma containing elevated sMICA and TGFb 1 markedly impaired NKG2D-dependent cytotoxicity against HNSCC cells upon incubation with patient-derived and IL-2 activated NK cells vs. those derived from healthy donors. Decreased antitumor recognition was accompanied by reduced NKG2D expression on the NK cell surface and an enhanced caspase-3 activity. In-vitro blocking and neutralization experiments demonstrated a synergistic negative impact of sMICA and TGFb 1 on NK cell functionality. Although we previously showed the feasibility and safety of transfer of allogeneic donor NK cells in a prior clinical study encompassing various leukemia and tumor patients, our present results suggest the need for caution regarding the sole use of adoptive NK cell transfer. The presence of soluble NKG2D ligands in the plasma of HNSCC patients and the decreased NK cell cytotoxicity due to several factors, especially TGFb 1 , indicates timely depletion of these immunosuppressing molecules may promote NK cell-based immunotherapy.

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Section: Introductionmentioning

confidence: 59%

Increased sMICA and TGFβ ₁ levels in HNSCC patients impair NKG2D-dependent functionality of activated NK cells

et al. 2015

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“…23 The incidence of SCC has been increasing faster and faster. 24 In the US, there were 53,640 new cases and 11,520 deaths due to SCC of the head and neck in 2013.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic antitumor efficacy of tumor-derived autophagosome (DRibble) vaccine on head and neck cancer

Su¹,

Luo²,

Xie³

et al. 2015

IJN

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Purpose Vaccines play important roles in antitumor biotherapy. Autophagy in tumor cells plays a critical role in depredating proteins, including tumor-specific antigens and tumor-associated antigens. We aimed to induce and collect tumor-derived autophagosomes (DRibbles) from tumor cells as a novel antitumor vaccine by inhibiting the functions of proteasomes and lysosomes. Materials and methods DRibbles were prepared and their morphological and autophagic properties characterized. Dendritic cells (DCs) generated from the bone marrow monocytes of mice were cocultured with DRibbles, then surface molecules of DCs and B cells, as well as apoptosis of DCs, were determined by flow cytometry. Meanwhile, functional properties of the DRibble-DCs were examined by mixed lymphocyte reactions and animal experiments. Results The diameter of autophagic nanoparticles with spherical and double-membrane structure was between 200 nm and 500 nm. DRibbles resulted in the upregulation of costimulatory molecules CD40 and CD86 as well as major histocompatibility complex (MHC)-I molecules on DCs, but not MHC-II. The expressions of CD40, CD80, and CD86 and that of MHC-II molecules on B cells were also upregulated. Moreover, suppression of tumor growth and lifetime prolongation was observed in DRibble-DC-vaccinated tumor-bearing mice. Conclusion Our results demonstrate that naïve T cells can be activated effectively by DC cross-presenting antigens on upregulated MHC-I, suggesting that DRibbles be deployed as an effective antitumor vaccine for head and neck cancer immunotherapy in clinical trials.

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“…5,6 In this process, neoplastic cells recruit different cell types that are able to suppress the immune response in the tumor microenvironment, particularly regulatory T (Treg) cells. 5 Treg cells are derived from the lymphocyte lineage that constitutively expresses CD4, CD25, and the nuclear transcription factor -forkhead box P3 (FoxP3).…”

Section: Introductionmentioning

confidence: 99%

Immunohistochemical analysis of FoxP3+ regulatory T cells in lower lip squamous cell carcinomas

et al. 2016

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The aim of this study was to determine the number of FoxP3+ regulatory T (Treg) cells in the microenvironment of lower lip squamous cell carcinomas (LLSCCs) and to correlate the findings with clinicopathological parameters (tumor size/extent, regional lymph node metastasis, clinical stage, and histopathological grade of malignancy). Fifty cases of LLSCC were selected. Lymphocytes exhibiting nuclear immunostaining for FoxP3 were quantified in 10 microscopic fields at the deep invasive front of LLSCCs. The results were analyzed statistically using the nonparametric Mann-Whitney test and Fisher's exact test. FoxP3+ lymphocytes were observed in all cases studied. The number of these cells tended to be higher in smaller tumors, tumors without regional lymph node metastasis, and tumors in early clinical stages, but the difference was not statistically significant (p > 0.05). Low-grade tumors contained a larger number of

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Immune Suppression in Head and Neck Cancers: A Review

Cited by 155 publications

References 170 publications

Increased sMICA and TGFβ ₁ levels in HNSCC patients impair NKG2D-dependent functionality of activated NK cells

Increased sMICA and TGFβ ₁ levels in HNSCC patients impair NKG2D-dependent functionality of activated NK cells

Therapeutic antitumor efficacy of tumor-derived autophagosome (DRibble) vaccine on head and neck cancer

Immunohistochemical analysis of FoxP3+ regulatory T cells in lower lip squamous cell carcinomas

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Immune Suppression in Head and Neck Cancers: A Review

Cited by 155 publications

References 170 publications

Increased sMICA and TGFβ 1 levels in HNSCC patients impair NKG2D-dependent functionality of activated NK cells

Increased sMICA and TGFβ 1 levels in HNSCC patients impair NKG2D-dependent functionality of activated NK cells

Therapeutic antitumor efficacy of tumor-derived autophagosome (DRibble) vaccine on head and&nbsp;neck cancer

Immunohistochemical analysis of FoxP3+ regulatory T cells in lower lip squamous cell carcinomas

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Increased sMICA and TGFβ ₁ levels in HNSCC patients impair NKG2D-dependent functionality of activated NK cells

Increased sMICA and TGFβ ₁ levels in HNSCC patients impair NKG2D-dependent functionality of activated NK cells

Therapeutic antitumor efficacy of tumor-derived autophagosome (DRibble) vaccine on head and neck cancer