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Oncoimmunology. 2015 Jun 5;4(7):e1058597. eCollection 2015 Jul.

Colorectal cancer: the first neoplasia found to be under immunosurveillance and the last one to respond to immunotherapy?

Author information

1
INSERM; U1138 ; Paris, France ; Université Paris Descartes/Paris V; Sorbonne Paris Cité ; Paris, France ; Université Pierre et Marie Curie/Paris VI ; Paris, France ; Equipe 11 labellisée Ligue contre le Cancer; Center de Recherche des Cordeliers ; Paris, France ; Metabolomics and Cell Biology Platforms; Gustave Roussy Comprehensive Cancer Institute ; Villejuif, France ; Pôle de Biologie, Hôpital Européen Georges Pompidou; AP-HP ; Paris, France.
2
INSERM; U1138 ; Paris, France ; Université Paris Descartes/Paris V; Sorbonne Paris Cité ; Paris, France ; Université Pierre et Marie Curie/Paris VI ; Paris, France ; Equipe 11 labellisée Ligue contre le Cancer; Center de Recherche des Cordeliers ; Paris, France ; Gustave Roussy Comprehensive Cancer Institute ; Villejuif, France.
3
Gustave Roussy Comprehensive Cancer Institute ; Villejuif, France ; INSERM; U1015; Equipe 11 labellisée Ligue contre le Cancer ; Villejuif, France ; Center of Clinical Investigations in Biotherapies of Cancer 507 (CICBT507) ; Villejuif, France ; Université Paris Sud/Paris XI; Le Kremlin-Bicêtre , France.
4
INSERM; U1138 ; Paris, France ; Université Paris Descartes/Paris V; Sorbonne Paris Cité ; Paris, France ; Université Pierre et Marie Curie/Paris VI ; Paris, France ; Equipe 11 labellisée Ligue contre le Cancer; Center de Recherche des Cordeliers ; Paris, France.

Abstract

The first study demonstrating that human colorectal carcinoma (CRC) is under robust immunosurveillance was published a decade ago. Today, it is clear that CRC patients with Stage III lesions abundantly infiltrated by effector memory T cells have a better prognosis than subjects with Stage I neoplasms exhibiting no or poor immune infiltration. Thus, immunological parameters have a superior prognostic value for CRC patients than TNM staging or the Dukes classification. In spite of the fact that CRC is the first neoplasia found to be under immunological control, most attempts made so far to cure this malignancy with immunotherapy have failed. With the exception of a minority of lesions characterized by microsatellite instability (MSI), CRC seems to be insensitive to the blockade of immunological checkpoints with monoclonal antibodies (mAbs) specific for cytotoxic T lymphocyte-associated protein 4 (CTLA4), programmed cell death 1 (PDCD1, best known as PD-1) and the PD-1 ligand CD274 (best known as PD-L1). Thus, CRC stands in contrast with an increasing number of malignancies that respond to checkpoint blockers. Efforts should therefore be dedicated to the development of strategies to (re)instate immunosurveillance in patients with MSI- CRC, perhaps based on the identification of novel, locally relevant immunological checkpoints.

KEYWORDS:

CTLA4; PD-1; PD-L1; ipilimumab; nivolumab; pembrolizumab

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