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
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Radiation Oncology
Published in: Radiation Oncology 1/2016

Open Access 01-12-2016 | Research

Feasibility study of DCs/CIKs combined with thoracic radiotherapy for patients with locally advanced or metastatic non-small-cell lung cancer

Authors: Luping Zhang, Yanmei Xu, Jie Shen, Feng He, Dan Zhang, Zhengtang Chen, Yuzhong Duan, Jianguo Sun

Published in: Radiation Oncology | Issue 1/2016

Login to get access

Abstract

Background

The combination of dendritic cells (DCs) and cytokine-induced killer cells (CIKs) can induce the anti-tumor immune response and radiotherapy may promote the activity. We aimed to explore the feasibility of DCs/CIKs combined with thoracic radiotherapy (TRT) for patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC).

Method

In this study, patients with unresectable stage III/IV NSCLC and an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0–2 and previously receiving two or more cycles of platinum-based doublet chemotherapy without disease progression received TRT plus DCs/CIKs or TRT alone until disease progression or unacceptable toxicity. The primary endpoint was median progression-free survival (mPFS). In treatment group, patients received four-cycle autologous DCs/CIKs infusion starting from the 6th fraction of irradiation.

Results

From Jan 13, 2012 to June 30, 2014, 82 patients were enrolled, with 21 patients in treatment group and 61 in control group. The mPFS in treatment group was longer than that in control group (330 days vs 233 days, hazard ratio 0.51, 95 % CI 0.27–1.0, P < 0.05), and the objective response rate (ORR) of treatment group (47.6 %) was significantly higher that of control group (24.6 %, P < 0.05). There was no significant difference in disease control rate (DCR) and median overall survival (mOS) between two groups (P > 0.05). The side effects in treatment group were mild and there was no treatment-related deaths.

Conclusion

The combination of DCs/CIKs with TRT could be a feasible regimen in treating locally advanced or metastatic NSCLC patients. Further investigation of the regimen is warranted.
Literature
1.
Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. International journal of cancer. Journal international du cancer. 2015;136(5):359-86.
2.
Brodowicz T, Krzakowski M, Zwitter M, Tzekova V, Ramlau R, Ghilezan N, et al. Cisplatin and gemcitabine first-line chemotherapy followed by maintenance gemcitabine or best supportive care in advanced non-small cell lung cancer: a phase III trial. Lung Cancer. 2006;52(2):155–63.CrossRefPubMed
3.
Allemani C, Weir HK, Carreira H, Harewood R, Spika D, Wang XS, et al. Global surveillance of cancer survival 1995-2009: analysis of individual data for 25676887 patients from 279 population-based registries in 67 countries. Lancet. 2015;385(9972):977-1010.
4.
Panakis N, McNair HA, Christian JA, Mendes R, Symonds-Tayler JR, Knowles C, et al. Defining the margins in the radical radiotherapy of non-small cell lung cancer (NSCLC) with active breathing control (ABC) and the effect on physical lung parameters. Radioth Oncol. 2008;87(1):65–73.CrossRef
5.
Apetoh L, Ghiringhelli F, Tesniere A, Obeid M, Ortiz C, Criollo A, et al. Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nat Med. 2007;13(9):1050–9.CrossRefPubMed
6.
Liao YP, Wang CC, Schaue D, Iwamoto KS, McBride WH. Local irradiation of murine melanoma affects the development of tumour-specific immunity. Immunology. 2009;128(1 Suppl):e797–804.CrossRefPubMedPubMedCentral
7.
Gupta A, Probst HC, Vuong V, Landshammer A, Muth S, Yagita H, et al. Radiotherapy promotes tumor-specific effector CD8+ T cells via dendritic cell activation. J Immunol. 2012;189(2):558–66.CrossRefPubMed
8.
Gameiro SR, Jammeh ML, Wattenberg MM, Tsang KY, Ferrone S, Hodge JW. Radiation-induced immunogenic modulation of tumor enhances antigen processing and calreticulin exposure, resulting in enhanced T-cell killing. Oncotarget. 2014;5(2):403–16.CrossRefPubMedPubMedCentral
9.
Chi KH, Liu SJ, Li CP, Kuo HP, Wang YS, Chao Y, et al. Combination of conformal radiotherapy and intratumoral injection of adoptive dendritic cell immunotherapy in refractory hepatoma. J Immunother. 2005;28(2):129–35.CrossRefPubMed
10.
Friedman EJ. Immune modulation by ionizing radiation and its implications for cancer immunotherapy. Curr Pharm Design. 2002;8(19):1765–80.CrossRef
11.
Finkelstein SE, Timmerman R, McBride WH, Schaue D, Hoffe SE, Mantz CA, et al. The confluence of stereotactic ablative radiotherapy and tumor immunology. Clin Dev Immunol. 2011;2011:439752.CrossRefPubMedPubMedCentral
12.
Villadangos JA, Schnorrer P. Intrinsic and cooperative antigen-presenting functions of dendritic-cell subsets in vivo. Nat Rev Immunol. 2007;7(7):543–55.CrossRefPubMed
13.
14.
Sangiolo D, Mesiano G, Carnevale-Schianca F, Piacibello W, Aglietta M, Cignetti A. Cytokine induced killer cells as adoptive immunotherapy strategy to augment graft versus tumor after hematopoietic cell transplantation. Expert Opin Biol Th. 2009;9(7):831–40.CrossRef
15.
Toomey PG, Vohra NA, Ghansah T, Sarnaik AA, Pilon-Thomas SA. Immunotherapy for gastrointestinal malignancies. Cancer Control. 2013;20(1):32–42.PubMedPubMedCentral
16.
Cui Y, Yang X, Zhu W, Li J, Wu X, Pang Y. Immune response, clinical outcome and safety of dendritic cell vaccine in combination with cytokine-induced killer cell therapy in cancer patients. Oncol Lett. 2013;6(2):537–41.PubMedPubMedCentral
17.
The Japan Lung Cancer Society. General rule for clinical and pathological record of lung cancer. 7th ed. Tokyo: Kanehara Press; 2010.
18.
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228–47.CrossRefPubMed
19.
Nicol AJ, Tazbirkova A, Nieda M. Comparison of clinical and immunological effects of intravenous and intradermal administration of alpha-galactosylceramide (KRN7000)-pulsed dendritic cells. Clin Cancer Res. 2011;17(15):5140–51.CrossRefPubMed
20.
Zhang SN, Choi IK, Huang JH, Yoo JY, Choi KJ, Yun CO. Optimizing DC vaccination by combination with oncolytic adenovirus coexpressing IL-12 and GM-CSF. Mol Ther. 2011;19(8):1558–68.CrossRefPubMedPubMedCentral
21.
Ma Y, Zhang Z, Tang L, Xu YC, Xie ZM, Gu XF, et al. Cytokine-induced killer cells in the treatment of patients with solid carcinomas: a systematic review and pooled analysis. Cytotherapy. 2012;14(4):483–93.CrossRefPubMed
22.
Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. New Engl J Med. 2010;363(5):411–22.CrossRefPubMed
23.
24.
Szyszka-Barth K, Ramlau K, Gozdzik-Spychalska J, Spychalski L, Bryl M, Golda-Gocka I, et al. Actual status of therapeutic vaccination in non-small cell lung cancer. Contemp Oncol (Pozn). 2014;18(2):77–84.
25.
Mukherji B, Chakraborty NG, Yamasaki S, Okino T, Yamase H, Sporn JR, et al. Induction of antigen-specific cytolytic T cells in situ in human melanoma by immunization with synthetic peptide-pulsed autologous antigen presenting cells. Proc Natl Acad Sci U S A. 1995;92(17):8078–82.CrossRefPubMedPubMedCentral
26.
Draube A, Klein-Gonzalez N, Mattheus S, Brillant C, Hellmich M, Engert A, et al. Dendritic cell based tumor vaccination in prostate and renal cell cancer: a systematic review and meta-analysis. PLoS One. 2011;6(4):e18801.CrossRefPubMedPubMedCentral
27.
Engell-Noerregaard L, Hansen TH, Andersen MH, Thor SP, Svane IM. Review of clinical studies on dendritic cell-based vaccination of patients with malignant melanoma: assessment of correlation between clinical response and vaccine parameters. Cancer Immunol Immun. 2009;58(1):1–14.CrossRef
28.
Small EJ, Fratesi P, Reese DM, Strang G, Laus R, Peshwa MV, et al. Immunotherapy of hormone-refractory prostate cancer with antigen-loaded dendritic cells. Clin Oncol. 2000;18(23):3894–903.
29.
Rosenberg SA, Restifo NP, Yang JC, Morgan RA, Dudley ME. Adoptive cell transfer: a clinical path to effective cancer immunotherapy. Nat Rev Cancer. 2008;8(4):299–308.CrossRefPubMedPubMedCentral
30.
Wang D, Zhang B, Gao H, Ding G, Wu Q, Zhang J, et al. Clinical research of genetically modified dendritic cells in combination with cytokine-induced killer cell treatment in advanced renal cancer. BMC Cancer. 2014;14(1):251.CrossRefPubMedPubMedCentral
31.
Lugade AA, Moran JP, Gerber SA, Rose RC, Frelinger JG, Lord EM. Local radiation therapy of B16 melanoma tumors increases the generation of tumor antigen-specific effector cells that traffic to the tumor. J Immunol. 2005;174(12):7516–23.CrossRefPubMed
32.
Garnett CT, Palena C, Chakraborty M, Tsang KY, Schlom J, Hodge JW. Sublethal irradiation of human tumor cells modulates phenotype resulting in enhanced killing by cytotoxic T lymphocytes. Cancer Res. 2004;64(21):7985–94.CrossRefPubMed
33.
Chakraborty M, Wansley EK, Carrasquillo JA, Yu S, Paik CH, Camphausen K, et al. The use of chelated radionuclide (samarium-153-ethylenediaminetetramethylenephosphonate) to modulate phenotype of tumor cells and enhance T cell-mediated killing. Clin Cancer Res. 2008;14(13):4241–9.CrossRefPubMedPubMedCentral
34.
Kwilas AR, Donahue RN, Bernstein MB, Hodge JW. In the field: exploiting the untapped potential of immunogenic modulation by radiation in combination with immunotherapy for the treatment of cancer. Front Oncol. 2012;2:104.CrossRefPubMedPubMedCentral
35.
Hodge JW, Sharp HJ, Gameiro SR. Abscopal regression of antigen disparate tumors by antigen cascade after systemic tumor vaccination in combination with local tumor radiation. Cancer Biother Radio. 2012;27(1):12–22.CrossRef
36.
Muhonen T, Hahka-Kemppinen M, Pakkala S, Pyrhonen S. Decreasing CD4/CD8 ratio during prolonged four-drug chemotherapy plus interferon treatment for metastatic melanoma. J Immunol. 1994;15(1):67–73.
37.
Yang L, Ng KY, Lillehei KO. Cell-mediated immunotherapy: a new approach to the treatment of malignant glioma. Cancer Control. 2003;10(2):138–47.PubMed
38.
Demaria S, Kawashima N, Yang AM, Devitt ML, Babb JS, Allison JP, et al. Immune-mediated inhibition of metastases after treatment with local radiation and CTLA-4 blockade in a mouse model of breast cancer. Clin Cancer Res. 2005;11(2 Pt 1):728–34.PubMed
39.
Deng L, Liang H, Burnette B, Beckett M, Darga T, Weichselbaum RR, et al. Irradiation and anti-PD-L1 treatment synergistically promote antitumor immunity in mice. J Clin Invest. 2014;124(2):687–95.CrossRefPubMedPubMedCentral
Metadata
Title
Feasibility study of DCs/CIKs combined with thoracic radiotherapy for patients with locally advanced or metastatic non-small-cell lung cancer
Authors
Luping Zhang
Yanmei Xu
Jie Shen
Feng He
Dan Zhang
Zhengtang Chen
Yuzhong Duan
Jianguo Sun
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Radiation Oncology / Issue 1/2016
Electronic ISSN: 1748-717X
DOI
https://doi.org/10.1186/s13014-016-0635-5

Other articles of this Issue 1/2016

Radiation Oncology 1/2016 Go to the issue

Research

Early clinical experience utilizing scintillator with optical fiber (SOF) detector in clinical boron neutron capture therapy: its issues and solutions

Research

Lungtech, a phase II EORTC trial of SBRT for centrally located lung tumours – a clinical physics perspective

Research

Temporo-spatial cell-cycle kinetics in HeLa cells irradiated by Ir-192 high dose-rate remote afterloading system (HDR-RALS)

Research

Benefits of stereotactic ablative radiotherapy combined with incomplete transcatheter arterial chemoembolization in hepatocellular carcinoma

Research

Evaluation of daily patient positioning for radiotherapy with a commercial 3D surface-imaging system (Catalyst™)

Research

Radiomics based targeted radiotherapy planning (Rad-TRaP): a computational framework for prostate cancer treatment planning with MRI