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Bittoni et al. J Cancer Metastasis Treat 2018;4:55 Journal of Cancer
DOI: 10.20517/2394-4722.2018.37 Metastasis and Treatment

Review Open Access

Immunotherapy in colorectal cancer treatment:
actual landscape and future perspectives

Alessandro Bittoni, Valeria Sotte, Tania Meletani, Luca Cantini, Riccardo Giampieri, Rossana Berardi

Clinica Oncologica, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti di Ancona, Ancona
60126, Italy.
Correspondence to: Dr. Rossana Berardi, Clinica Oncologica, Università Politecnica delle Marche, Azienda Ospedaliero-
Universitaria Ospedali Riuniti di Ancona, Via Conca 71, Ancona 60126, Italy. E-mail: rossana.berardi.it@gmail.com
How to cite this article: Bittoni A, Sotte V, Meletani T, Cantini L, Giampieri R, Berardi R. Immunotherapy in colorectal cancer
treatment: actual landscape and future perspectives. J Cancer Metastasis Treat 2018;4:55.
http://dx.doi.org/10.20517/2394-4722.2018.37
Received: 13 Jun 2018 First Decision: 10 Jul 2018 Revised: 16 Sep 2018 Accepted: 9 Oct 2018 Published: 26 Oct 2018

Science Editor: Guo-Feng Xie Copy Editor: Cui Yu Production Editor: Zhong-Yu Guo

Abstract
Colorectal cancer (CRC) represents the second most common cancer in Europe with marked differences
in prognosis and response to treatments. In the past years research showed emerging interest in genomic
and immunologic fields. The clinical heterogeneity, that occurs during the pathogenesis of CRC, is driven
by chromosomal alterations and defective function of DNA mismatch repair genes. CRC is classified in four
consensus molecular subtypes (CMS) with different immunogenic characteristics and prognosis. CMS1
microsatellite instable (MSI)-like and CMS4, both characterized by high levels of immune infiltration, are
recognized as the most immunogenic subtypes, even though functional characteristic leading to different
prognosis are reported. In particular, MSI tumors have been identified as the best candidates for immunotherapy
treatment and a number of studies have evaluated the efficacy of anti-programmed cell death ligand-1 (PDL-1)
and anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) in this setting. However, literature data show that
the majority of patients with CRC have microsatellite stable (MSS) tumors and this status seems related to lower
response to PDL-1/programmed cell death-1 or CTLA4 blockade. The aim of this paper is to investigate the role of
immunotherapy in MSI and MSS CRC.

Keywords: Colorectal cancer, immunotherapy, microsatellite instable, microsatellite stable mismatch repair,
prognosis

INTRODUCTION
Colorectal cancer (CRC) represents the second most common cancer in Europe with significant
heterogeneity in prognosis and response to treatment. Prognostic factors include stage of disease, site of

© The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0
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