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Oncoimmunology. 2014 Jan 1;3(1):e27884. Epub 2014 Feb 27.

Immune-related gene signatures predict the outcome of neoadjuvant chemotherapy.

Author information

1
Université Paris Descartes/Paris V, Sorbonne Paris Cité; Paris, France ; Equipe 11 labellisée Ligue Nationale contre le Cancer ; Cordeliers Research Center; INSERM U1138; Paris, France.
2
Metabolomics and Cell Biology Platforms; Gustave Roussy Cancer Campus; Villejuif, France.
3
Université Paris Descartes/Paris V, Sorbonne Paris Cité; Paris, France ; Laboratory of Integrative Cancer Immunology; INSERM U1138; Paris, France ; Cordeliers Research Center; Université Pierre et Marie Curie Paris 6; Paris, France.
4
INSERM U1015; Villejuif, France ; Faculté de Médecine; Université Paris Sud; Le Kremlin Bicêtre, France ; Center of Clinical Investigations in Biotherapies of Cancer (CICBT) 507; Villejuif, France.
5
Université Paris Descartes/Paris V, Sorbonne Paris Cité; Paris, France ; Equipe 11 labellisée Ligue Nationale contre le Cancer ; Cordeliers Research Center; INSERM U1138; Paris, France ; Metabolomics and Cell Biology Platforms; Gustave Roussy Cancer Campus; Villejuif, France ; INSERM, U848; Villejuif, France ; Pôle de Biologie; Hôpital Européen Georges Pompidou, AP-HP; Paris, France.

Abstract

There is ample evidence that neoadjuvant chemotherapy of breast carcinoma is particularly efficient if the tumor presents signs of either a pre-existent or therapy-induced anticancer immune response. Antineoplastic chemotherapies are particularly beneficial if they succeed in inducing immunogenic cell death, hence converting the tumor into its own therapeutic vaccine. Immunogenic cell death is characterized by a pre-mortem stress response including endoplasmic reticulum stress and autophagy. Based on these premises, we attempted to identify metagenes that reflect an intratumoral immune response or local stress responses in the transcriptomes of breast cancer patients. No consistent correlations between immune- and stress-related metagenes could be identified across several cohorts of patients, representing a total of 1045 mammary carcinomas. Moreover, few if any, of the stress-relevant metagenes influenced the probability of pathological complete response to chemotherapy. In contrast, several immune-relevant metagenes had a significant positive impact on response rates. This applies in particular to a CXCL13-centered, highly reproducible metagene signature reflecting the intratumoral presence of interferon-γ-producing T cells.

KEYWORDS:

autophagy; breast cancer; colorectal cancer; endoplasmic stress; immunogenic cell death; tumor-infiltrating lymphocytes

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