Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Cancer Immunology, Immunotherapy
Published in: Cancer Immunology, Immunotherapy 10/2010

01-10-2010 | Original Article

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

Authors: Kouichi Kobayashi, Yuriko Tanaka, Shigetoshi Horiguchi, Shouji Yamamoto, Nakayama Toshinori, Akira Sugimoto, Yoshitaka Okamoto

Published in: Cancer Immunology, Immunotherapy | Issue 10/2010

Login to get access

Abstract

Background

Cancer immunotherapy with NKT cells is a potential new treatment strategy for advanced head and neck cancer. NKT cell therapy is promising due to its unique anti-tumor activity and higher degree of safety compared to current therapies. Radiotherapy is indispensable as a standard treatment for advanced head and neck cancer. To elucidate the possibility of using NKT cells as an adjuvant immunotherapy with radiotherapy, we examined the effect of radiotherapy on NKT cells in patients with head and neck cancer.

Methods

The number, IFN-γ production and proliferation capacity of NKT cells were analyzed before and after 50 Gy radiation therapy in 12 patients with stage IV head and neck squamous cell carcinoma. The cytotoxic activity of NKT cells was examined in vitro.

Results

The number of NKT cells in the blood varied widely between patients. After radiation therapy, the population of CD3 T cells decreased significantly, while the NKT cell population remained stable. The number of NKT cells was the same after radiation therapy as before. IFN-γ production from NKT cells collected just after radiotherapy was impaired after stimulation with exogenous ligand, but the proliferative responses of these NKT cells was enhanced in comparison to those collected before radiation therapy. Furthermore, the proliferated NKT cells displayed a significant level of anti-tumor activity.

Conclusion

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.
Literature
1.
Hainsworth JD, Meluch AA, McClurkan S, Gray JR, Stroup SL, Burris HA III, Yardley DA, Bradof JE, Yost K, Ellis JK, Greco FA (2002) Induction paclitaxel, carboplatin, and infusional 5-FU followed by concurrent radiation therapy and weekly paclitaxel/carboplatin in the treatment of locally advanced head and neck cancer: a phase II trial of the Minnie Pearl Cancer Research Network. Cancer J 8:298–300CrossRef
2.
Zelefsky MJ, Harrison LB, Fass DE, Armstrong J, Spiro RH, Shah JP, Strong EW (1993) Postoperative radiotherapy for oral cavity cancers: impact of anatomic subsite on treatment outcome. Head Neck 12:470–475CrossRef
3.
Clark J, Li W, Smith G, Shannon K, Clifford A, McNeil E, Gao K, Jackson M, Mo Tin M, O’Brien C (2005) Outcome of treatment for advanced cervical metastatic squamous cell carcinoma. Head Neck 27:87–94CrossRefPubMed
4.
Hicks WL Jr, Loree TR, Garcia RI, Maamoun S, Marshall D, Orner JB, Bakamjian VY, Shedd DP (1997) Squamous cell carcinoma of the floor of mouth: a 20-year review. Head Neck 19:400–405CrossRefPubMed
5.
Metelmann HR (2000) Chemotherapy and radiochemotherapy in tumors of the head–neck area. Mund Kiefer Gesichtschir 4(suppl 1):S155–S159CrossRefPubMed
6.
Wanebo HJ, Glicksman AS, Landman C, Slotman G, Doolittle C, Clark J, Koness RJ (1995) Preoperative cisplatin and accelerated hyperfractionated radiation induces high tumor response and control rates in patients with advanced head and neck cancer. Am J Surg 170:512–516CrossRefPubMed
7.
8.
Cortesina G, De Stefani A, Sacchi M, Rosso S, Galeazzi E (1993) Immunomodulation therapy for squamous cell carcinoma of the head and neck. Head Neck 15:266–270CrossRefPubMed
9.
Gualde N, Goodwin JS (1984) Effect of irradiation on human T-cell proliferation: low dose irradiation stimulates mitogen-induced proliferation and function of the suppressor/cytotoxic T-cell subset. Cell Immunol 84:439–445CrossRefPubMed
10.
Rose H, Moldenhauer H, Kehrberg G (1985) Lymphocyte damage caused by ionizing radiation. Radiobiol Radiother 26:289–297
11.
Vicari AP, Zlotnik A (1996) Mouse NK1.1+ T cells: a new family of T cells. Immunol Today 17:71–76CrossRefPubMed
12.
Taniguchi M, Koseki H, Tokuhisa T, Masuda K, Sato H, Kondo E, Kawano T, Cui J, Perkes A, Koyasu S, Makino Y (1996) Essential requirement of an invariant Vα14 T cell antigen receptor expression in the development of natural killer T cells. Proc Natl Acad Sci USA 93:11025–11028CrossRefPubMed
13.
Bendelac A, Rivera MN, Park SH, Roark JH (1997) Mouse CD1-specific NK1 T cells: development, specificity, and function. Annu Rev Immunol 15:535–562CrossRefPubMed
14.
Hameg A, Apostolou I, Leite-De-Moraes M, Gombert JM, Garcia C, Koezuka Y, Bach JF, Herbelin A (2000) A subset of NKT cells that lacks the NK1.1 marker, expresses CD1d molecules, and autopresents the alpha-galactosylceramide antigen. J Immunol 165:4917–4926PubMed
15.
Nicol A, Nieda M, Koezuka Y, Porcelli S, Suzuki K, Tadokoro K, Durrant S, Juji T (2000) Human invariant valpha24+ natural killer T cells activated by alpha-galactosylceramide (KRN7000) have cytotoxic anti-tumor activity through mechanisms distinct from T cells and natural killer cells. Immunology 99(2):229–234CrossRefPubMed
16.
Seino K, Motohashi S, Fujisawa T, Nakayama T, Taniguchi M (2006) Natural killer T cell-mediated antitumor immune responses and their clinical applications. Cancer Sci 97:807–812CrossRefPubMed
17.
Molling JW, Kölgen W, van der Vliet HJ, Boomsma MF, Kruizenga H, Smorenburg CH, Molenkamp BG, Langendijk JA, Leemans CR, von Blomberg BM, Scheper RJ, van den Eertwegh AJ (2005) Peripheral blood IFN-gamma-secreting Valpha24 + Vbeta11 + NKT cell numbers are decreased in cancer patients independent of tumor type or tumor load. Int J Cancer 116:87–93CrossRefPubMed
18.
Motohashi S, Ishikawa A, Ishikawa E, Otsuji M, Iizasa T, Hanaoka H, Shimizu N, Horiguchi S, Okamoto Y, Fujii S, Taniguchi M, Fujisawa T, Nakayama T (2006) A phase I study of in vitro expanded natural killer T cells in patients with advanced and recurrent non-small cell lung cancer. Clin Cancer Res 12:6079–6086CrossRefPubMed
19.
Uchida T, Horiguchi S, Tanaka Y, Yamamoto H, Kunii N, Motohashi S, Taniguchi M, Nakayama T, Okamoto Y (2008) Phase I study of alpha-galactosylceramide-pulsed antigen presenting cells administration to the nasal submucosa in unresectable or recurrent head and neck cancer. Cancer Immunol Immunother 57:337–345CrossRefPubMed
20.
Knii N, Horiguchi S, Motohashi S, Yamamoto H, Ueno N, Yamamoto S, Sakurai D, Taniguchi M, Nakayama T, Okamoto Y (2009) Combination therapy of in vitro-expanded natural killer T cells and alpha-galactosylceramide-pulsed antigen-presenting cells in patients with recurrent head and neck carcinoma. Cancer Sci 100:1092–1098CrossRef
21.
Ogawa Y, Kobayashi T, Nishioka A, Kariya S, Ohnishi T, Hamasato S, Seguchi H, Yoshida S (2004) Reactive oxygen species-producing site in radiation-induced apoptosis of human peripheral T cells: involvement of lysosomal membrane destabilization. Int J Mol Med 13:69–73PubMed
22.
Molling JW, Langius JA, Langendijk JA, Leemans CR, Bontkes HJ, van der Vliet HJ, von Blomberg BM, Scheper RJ, van den Eertwegh AJ (2007) Low levels of circulating invariant natural killer T cells predict poor clinical outcome in patients with head and neck squamous cell carcinoma. J Clin Oncol 25:862–868CrossRefPubMed
23.
Kajioka EH, Andres ML, Li J, Mao XW, Moyers MF, Nelson GA, Slater JM, Gridley DS (2000) Acute effects of whole-body proton irradiation on the immune system of the mouse. Radiat Res 153:587–594CrossRefPubMed
24.
Crough T, Purdie DM, Okai M, Maksoud A, Nieda M, Nicol AJ (2004) Modulation of human Valpha24(+)Vbeta11(+)NKT cells by age, malignancy and conventional anticancer therapy. Br J Cancer 91:1880–1886CrossRefPubMed
25.
Coquet JM, Chakravarti S, Kyparissoudis K, McNab FW, Pitt LA, McKenzie BS, Berzins SP, Smyth MJ, Godfrey DI (2008) Diverse cytokine production by NKT cell subsets and identification of an IL-17-producing CD4-NK1.1–NKT cell population. Proc Natl Acad Sci USA 105:11287–11292CrossRefPubMed
26.
Wu D, Xing GW, Poles MA, Horowitz A, Kinjo Y, Sullivan B, Bodmer-Narkevitch V, Plettenburg O, Kronenberg M, Tsuji M, Ho DD, Wong CH (2005) Bacterial glycolipids and analogs as antigens for CD1d-restricted NKT cells. Proc Natl Acad Sci USA 102:1351–1356CrossRefPubMed
27.
Fujii S, Shimizu K, Hemmi H, Steinman RM (2007) Innate Valpha14(+) natural killer T cells mature dendritic cells, leading to strong adaptive immunity. Immunol Rev 220:183–198CrossRefPubMed
28.
Goto M, Murakawa M, Kadoshima-Yamaoka K, Tanaka Y, Nagahira K, Fukuda Y, Nishimura T (2009) Murine NKT cells produce Th17 cytokine interleukin-22. Cell Immunol 254:81–84CrossRefPubMed
29.
Kitamura H, Ohta A, Sekimoto M, Sato M, Iwakabe K, Nakui M, Yahata T, Meng H, Koda T, Nishimura S, Kawano T, Taniguchi M, Nishimura T (2000) Alpha-galactosylceramide induces early B-cell activation through IL-4 production by NKT cells. Cell Immunol 199:37–42CrossRefPubMed
30.
Mignogna MD, Fedele S, Lo Russo L (2004) The world cancer report and the burden of oral cancer. Eur J Cancer Prev 13:139–142CrossRefPubMed
31.
Zhen W, Karnell LH, Hoffman HT, Funk GF, Buatti JM, Menck HR (2004) The national cancer data base report on squamous cell carcinoma of the base of tongue. Head Neck 26:660–674CrossRefPubMed
32.
Carvalho AL, Ikeda MK, Magrin J, Kowalski LP (2004) Trends of oral and oropharyngeal cancer survival over five decades in 3267 patients treated in a single institution. Oral Oncol 40:71–76CrossRefPubMed
33.
Sessions DG, Lenox J, Spector GJ, Chao C, Chaudry OA (2003) Analysis of treatment results for base of tongue cancer. Laryngoscope 113:1252–1261CrossRefPubMed
Metadata
Title
The effect of radiotherapy on NKT cells in patients with advanced head and neck cancer
Authors
Kouichi Kobayashi
Yuriko Tanaka
Shigetoshi Horiguchi
Shouji Yamamoto
Nakayama Toshinori
Akira Sugimoto
Yoshitaka Okamoto
Publication date
01-10-2010
Publisher
Springer-Verlag
Published in
Cancer Immunology, Immunotherapy / Issue 10/2010
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-010-0877-2

Other articles of this Issue 10/2010

Cancer Immunology, Immunotherapy 10/2010 Go to the issue

Focussed Research Review

The escape of cancer from T lymphocytes: immunoselection of MHC class I loss variants harboring structural-irreversible “hard” lesions

Focussed Research Review

Myeloid-derived suppressor cells: more mechanisms for inhibiting antitumor immunity

Original Article

Immunotherapy in high-risk chemotherapy-resistant patients with metastatic solid tumors and hematological malignancies using intentionally mismatched donor lymphocytes activated with rIL-2: a phase I study

Original Article

WT1 peptide vaccinations induce CD4 and CD8 T cell immune responses in patients with mesothelioma and non-small cell lung cancer

Original Article

Phase I study of bromohydrin pyrophosphate (BrHPP, IPH 1101), a Vγ9Vδ2 T lymphocyte agonist in patients with solid tumors

Letter to the editor

Response to the letter to the editors by Ottaiano et al.: “Cetuximab-dependent ADCC in cancer: dream or reality?”
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits