Skip to main content
Top
Published in: Cancer Immunology, Immunotherapy 5/2017

01-05-2017 | Original Article

Elevated basal antibody-dependent cell-mediated cytotoxicity (ADCC) and high epidermal growth factor receptor (EGFR) expression predict favourable outcome in patients with locally advanced head and neck cancer treated with cetuximab and radiotherapy

Authors: Laura Lattanzio, Nerina Denaro, Daniela Vivenza, Chiara Varamo, Giuliana Strola, Mirella Fortunato, Emmanuel Chamorey, Alberto Comino, Martino Monteverde, Cristiana Lo Nigro, Gerard Milano, Marco Merlano

Published in: Cancer Immunology, Immunotherapy | Issue 5/2017

Login to get access

Abstract

Background

Antibody-dependent cell-mediated cytotoxicity (ADCC) may contribute to the antitumor activity of cetuximab. However, the extent of this contribution is unclear. In this study, we investigated the impact of baseline ADCC on the outcome of patients with locally advanced squamous cell carcinoma treated with cetuximab and radiotherapy.

Methods

We determined baseline ADCC in 28 patients treated with cetuximab and radiotherapy and in 15 patients treated with chemoradiation. We linked the values observed with complete response and with overall survival. We also considered the role of epidermal growth factor receptor (EGFR) expression and studied the combined effect of EGFR and ADCC.

Results

We observed a wide range of baseline values of ADCC. Complete response did not correlate with either ADCC or EGFR expression. However, when ADCC and EGFR were considered together using a mixed score, they significantly correlated with achieving a complete response (p = 0.04). High baseline ADCC significantly correlated with outcome compared to low (p = 0.03), but not in patients treated without cetuximab. Patients showing high baseline levels of both ADCC and EGFR3+ achieved the best outcome compared to the others (p = 0.02).

Conclusions

In this study, patients treated with cetuximab and radiotherapy, showing high baseline of both ADCC and EGFR3+, have significant higher probability of achieving a complete response and a long overall survival compared to the others.
Literature
1.
go back to reference Dawood S, Broglio K, Buzdar AU et al (2009) Prognosis of women with metastatic breast cancer by HER2 status and trastuzumab treatment: an institutional-based review. J Clin Oncol 28:92–98CrossRefPubMedPubMedCentral Dawood S, Broglio K, Buzdar AU et al (2009) Prognosis of women with metastatic breast cancer by HER2 status and trastuzumab treatment: an institutional-based review. J Clin Oncol 28:92–98CrossRefPubMedPubMedCentral
2.
go back to reference Boero S, Morabito A, Banelli B et al (2015) Analysis of in vitro ADCC and clinical response to trastuzumab: possible relevance of FcyRIIIA/FcyRIIA gene polymorphism and HER-2 expression levels on breast cancer cell lines. J Transl Med 13:324CrossRefPubMedPubMedCentral Boero S, Morabito A, Banelli B et al (2015) Analysis of in vitro ADCC and clinical response to trastuzumab: possible relevance of FcyRIIIA/FcyRIIA gene polymorphism and HER-2 expression levels on breast cancer cell lines. J Transl Med 13:324CrossRefPubMedPubMedCentral
3.
go back to reference Cartron G, Dacheux L, Salles G et al (2002) Therapeutic activity of humanized anti-CD20 monoclonal antibody and polymorphism in IgG Fc receptor FcgammaRIIIa gene. Blood 99:754–758CrossRefPubMed Cartron G, Dacheux L, Salles G et al (2002) Therapeutic activity of humanized anti-CD20 monoclonal antibody and polymorphism in IgG Fc receptor FcgammaRIIIa gene. Blood 99:754–758CrossRefPubMed
4.
go back to reference Maréchal R, De Schutter J, Nagy N, Demetter P, Lemmers A, Devière J, Salmon I, Tejpar S, Van Laethem JL (2010) Putative contribution of CD56 + positive cells in cetuximab treatment efficacy in first-line metastatic colorectal cancer patients. BMC Cancer 10:340CrossRefPubMedPubMedCentral Maréchal R, De Schutter J, Nagy N, Demetter P, Lemmers A, Devière J, Salmon I, Tejpar S, Van Laethem JL (2010) Putative contribution of CD56 + positive cells in cetuximab treatment efficacy in first-line metastatic colorectal cancer patients. BMC Cancer 10:340CrossRefPubMedPubMedCentral
5.
go back to reference Wagner S, Wittekindt C, Reuschenbach M, Hennig B, Thevarajah M, Würdemann N, Prigge ES, von Knebel Doeberitz M, Dreyer T, Gattenlöhner S, Klussmann JP (2016) CD56-positive lymphocyte infiltration in relation to human papillomavirus association and prognostic significance in oropharyngeal squamous cell carcinoma. Int J Cancer 138:2263–2273CrossRefPubMed Wagner S, Wittekindt C, Reuschenbach M, Hennig B, Thevarajah M, Würdemann N, Prigge ES, von Knebel Doeberitz M, Dreyer T, Gattenlöhner S, Klussmann JP (2016) CD56-positive lymphocyte infiltration in relation to human papillomavirus association and prognostic significance in oropharyngeal squamous cell carcinoma. Int J Cancer 138:2263–2273CrossRefPubMed
6.
go back to reference Monteverde M, Milano G, Strola G, Maffi M, Lattanzio L, Vivenza D, Tonissi F, Merlano M, Lo Nigro C (2015) The relevance of ADCC for EFGR targeting: a review of the literature and a clinically applicable method of assessment in patients. Crit Rev Oncol Hematol 95(2):179–190CrossRefPubMed Monteverde M, Milano G, Strola G, Maffi M, Lattanzio L, Vivenza D, Tonissi F, Merlano M, Lo Nigro C (2015) The relevance of ADCC for EFGR targeting: a review of the literature and a clinically applicable method of assessment in patients. Crit Rev Oncol Hematol 95(2):179–190CrossRefPubMed
7.
go back to reference Lo Nigro C, Ricci V, Vivenza D, Monteverde M, Strola G, Lucio F, Tonissi F, Miraglio E, Granetto C, Fortunato M, Merlano MC (2016) Evaluation of antibody-dependent cell-mediated cytotoxicity activity and cetuximab response in KRAS wilde-type colorectal cancer patients. World J Gastrointest Oncol 8:222–230CrossRefPubMedPubMedCentral Lo Nigro C, Ricci V, Vivenza D, Monteverde M, Strola G, Lucio F, Tonissi F, Miraglio E, Granetto C, Fortunato M, Merlano MC (2016) Evaluation of antibody-dependent cell-mediated cytotoxicity activity and cetuximab response in KRAS wilde-type colorectal cancer patients. World J Gastrointest Oncol 8:222–230CrossRefPubMedPubMedCentral
8.
go back to reference Mickel RA, Kessler DJ, Taylor JM, Lichtenstein A (1988) Natural killer cell cytotoxicity in the peripheral blood, cervical lymph nodes, and tumor of head and neck cancer patients. Cancer Res 48(17):5017–5022PubMed Mickel RA, Kessler DJ, Taylor JM, Lichtenstein A (1988) Natural killer cell cytotoxicity in the peripheral blood, cervical lymph nodes, and tumor of head and neck cancer patients. Cancer Res 48(17):5017–5022PubMed
9.
go back to reference Kono K, Takahashi A, Ichihara F, Sugai H, Fujii H, Matsumoto Y (2002) Impaired antibody-dependent cellular cytotoxicity mediated by herceptin in patients with gastric cancer. Cancer Res 62(20):5813–5817PubMed Kono K, Takahashi A, Ichihara F, Sugai H, Fujii H, Matsumoto Y (2002) Impaired antibody-dependent cellular cytotoxicity mediated by herceptin in patients with gastric cancer. Cancer Res 62(20):5813–5817PubMed
10.
go back to reference Taylor RJ, Saloura V, Jain A, Goloubeva O, Wong S, Kronsberg S, Nagilla M, Silpino L, de Souza J, Seiwert T, Vokes E, Villaflor V, Cohen EE (2015) Ex vivo antibody-dependent cellular cytotoxicity inducibility predicts efficacy of cetuximab. Cancer Immunol Res 3(5):567–574CrossRefPubMedPubMedCentral Taylor RJ, Saloura V, Jain A, Goloubeva O, Wong S, Kronsberg S, Nagilla M, Silpino L, de Souza J, Seiwert T, Vokes E, Villaflor V, Cohen EE (2015) Ex vivo antibody-dependent cellular cytotoxicity inducibility predicts efficacy of cetuximab. Cancer Immunol Res 3(5):567–574CrossRefPubMedPubMedCentral
12.
go back to reference Molling JW, Langius JAE, Langendijk JA et al (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 Molling JW, Langius JAE, Langendijk JA et al (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
13.
go back to reference Chen J, Feng Y, Lu L, Wang H, Dai L, Li Y, Zhang P (2012) Interferon-γ-induced PD-L1 surface expression on human oral squamous carcinoma via PKD2 signal pathway. Immunobiology 217(4):385–393CrossRefPubMed Chen J, Feng Y, Lu L, Wang H, Dai L, Li Y, Zhang P (2012) Interferon-γ-induced PD-L1 surface expression on human oral squamous carcinoma via PKD2 signal pathway. Immunobiology 217(4):385–393CrossRefPubMed
Metadata
Title
Elevated basal antibody-dependent cell-mediated cytotoxicity (ADCC) and high epidermal growth factor receptor (EGFR) expression predict favourable outcome in patients with locally advanced head and neck cancer treated with cetuximab and radiotherapy
Authors
Laura Lattanzio
Nerina Denaro
Daniela Vivenza
Chiara Varamo
Giuliana Strola
Mirella Fortunato
Emmanuel Chamorey
Alberto Comino
Martino Monteverde
Cristiana Lo Nigro
Gerard Milano
Marco Merlano
Publication date
01-05-2017
Publisher
Springer Berlin Heidelberg
Published in
Cancer Immunology, Immunotherapy / Issue 5/2017
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-017-1960-8

Other articles of this Issue 5/2017

Cancer Immunology, Immunotherapy 5/2017 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

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