The effect of radiotherapy on NKT cells in patients with advanced head and neck cancer

Kobayashi, K; Tanaka, Yuriko; Horiguchi, Susumu; Yamamoto, Sadamu; Nakayama, Toshinori; Sugimoto, Akira; Okamoto, Yoshitaka

doi:10.1007/s00262-010-0877-2

Cited by 17 publications

(10 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These results indicated that the administration of α-GalCer-pulsed APCs via the nasal submucosa was a better option for HNC patients. We also confirmed that the number and function of iNKT cells were not affected by radiation therapy, suggesting that iNKT cell based immunotherapy might be an adjuvant treatment of radiation therapy for advanced HNC patients ( 23 ).…”

Section: Introductionsupporting

confidence: 72%

Clinical Application of iNKT Cell-mediated Anti-tumor Activity Against Lung Cancer and Head and Neck Cancer

2018

View full text Add to dashboard Cite

Invariant natural killer T (iNKT) cells produce copious amounts of cytokines in response to T-cell receptor (TCR) stimulation by recognizing antigens such as α-galactosylceramide (α-GalCer) presented on CD1d; thus, orchestrating other immune cells to fight against pathogen infection and tumors. Because of their ability to induce strong anti-tumor responses and the convenience of their invariant TCR activated by a synthetic ligand, α-GalCer, iNKT cells have been intensively studied for application in immunotherapeutic approaches to treat cancer patients in the clinic. Here, we summarize the clinical trials of iNKT cell based immunotherapy for non-small cell lung cancer, and head and neck cancer. Although solid tumors are thought to be refractory to immunotherapeutic approaches, our clinical trials showed that the intravenous injection of α-GalCer-pulsed antigen presenting cells (APCs) activated endogenous iNKT cells and iNKT cell dependent responses. Moreover, an increase in the number of IFN-γ producing cells in PBMCs was associated with prolonged survival. The marked infiltration of iNKT cells and the accumulation of conventional T cells in the tumor microenvironment were also observed after the administration of α-GalCer-pulsed APCs and/or ex vivo activated iNKT cells. In cases of advanced head and neck squamous cell carcinoma, the increased accumulation of iNKT cells in the tumor microenvironment was correlated with objective clinical responses. We will also discuss potential combination therapies of iNKT cell based immunotherapy to achieve enhanced anti-tumor activity and provide better treatment options for these patients.

show abstract

Section: Introductionsupporting

confidence: 72%

Clinical Application of iNKT Cell-mediated Anti-tumor Activity Against Lung Cancer and Head and Neck Cancer

2018

View full text Add to dashboard Cite

show abstract

“…However, studies of firstdegree relatives of SLE patients suggest that iNKT cell dysfunction precedes autoimmunity, which is suggestive of a causative role in disease (14). Similarly, various solid-state and hematological cancer patients were shown to have reductions in iNKT cell numbers and function, which correlated inversely with prognosis (15)(16)(17)(18)(19)(20)(21). iNKT cells also were shown to play a regulatory role in other autoimmune disorders.…”

mentioning

confidence: 99%

Invariant NKT Cell Activation Is Potentiated by Homotypic trans-Ly108 Interactions

Baglaenko

Tleugabulova

Gracey

et al. 2017

The Journal of Immunology

View full text Add to dashboard Cite

Invariant NKT (iNKT) cells are innate lymphocytes that respond to glycolipids presented by the MHC class Ib molecule CD1d and are rapidly activated to produce large quantities of cytokines and chemokines. iNKT cell development uniquely depends on interactions between double-positive thymocytes that provide key homotypic interactions between signaling lymphocyte activation molecule (SLAM) family members. However, the role of SLAM receptors in the differentiation of iNKT cell effector subsets and activation has not been explored. In this article, we show that C57BL/6 mice containing the New Zealand Black locus have profound alterations in Ly108, CD150, and Ly9 expression that is associated with iNKT cell hyporesponsiveness. This loss of function was only apparent when dendritic cells and iNKT cells had a loss of SLAM receptor expression. Using small interfering RNA knockdowns and peptide-blocking strategies, we demonstrated that-Ly108 interactions between dendritic cells and iNKT cells are critical for robust activation. LY108 costimulation similarly increased human iNKT cell activation. Thus, in addition to its established role in iNKT cell ontogeny, Ly108 regulates iNKT cell function in mice and humans.

show abstract

“…As NKT cells are sharing some receptors and common features with T lymphocytes and NK cells they provide a functional link between the innate and adaptive antitumor immunity [35,36] and play crucial roles in immune regulation and surveillance against cancer [37]. Kobayashi et al described the ability of radiotherapy to improve proliferation and antitumor immunity of NKT cells [38]. In our SCCHN cohort, especially patients with locoregional recurrences, exhibited increased NKT cell levels at diagnosis which further increase throughout therapy as compared to controls.…”

Section: Discussionmentioning

confidence: 56%

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

View full text Add to dashboard Cite

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.

show abstract

The effect of radiotherapy on NKT cells in patients with advanced head and neck cancer

Abstract: NKT cells are relatively resistant to radiation and might therefore be suitable for adjuvant immunotherapy to eradicate remnant cancer cells in patients who have undergone radiation therapy.

Cited by 17 publications

References 31 publications

Clinical Application of iNKT Cell-mediated Anti-tumor Activity Against Lung Cancer and Head and Neck Cancer

Clinical Application of iNKT Cell-mediated Anti-tumor Activity Against Lung Cancer and Head and Neck Cancer

Invariant NKT Cell Activation Is Potentiated by Homotypic trans-Ly108 Interactions

Contact Info

Product

Resources

About