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Open AccessJournal ArticleDOI

The Immune Biology of Microsatellite-Unstable Cancer

Matthias Kloor, +1 more
- 01 Mar 2016 - 
- Vol. 2, Iss: 3, pp 121-133
TLDR
The current understanding of the immune biology of MSI cancers is summarized and new concepts and research directions to develop not only therapeutic treatments, but also preventive vaccines based on the MSI cancer genome landscapes are outlined.
Abstract
Deficient DNA mismatch repair (MMR) boosts the accumulation of frameshift mutations in genes encompassing coding microsatellites (cMS). This results in the translation of proteins with mutation-induced frameshift peptides (neoantigens) rendering microsatellite-unstable (MSI) cancers highly immunogenic. MSI cancers express a defined set of neoantigens resulting from functionally relevant driver mutations, which are shared by most MSI cancers. Patients with MSI cancers and healthy individuals affected by Lynch syndrome, an inherited predisposition for MSI cancers, develop specific immune responses against these neoantigens. In this review, we summarize our current understanding of the immune biology of MSI cancers and outline new concepts and research directions to develop not only therapeutic treatments, but also preventive vaccines based on the MSI cancer genome landscapes.

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Citations
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Journal ArticleDOI

Immunotherapy in colorectal cancer: rationale, challenges and potential.

TL;DR: Clinical development of immune checkpoint inhibition in CRC leading to regulatory approvals for the treatment of dMMR–MSI-H CRC is reviewed and new advances in expanding the efficacy of immunotherapy to early-stage CRC and CRC that is mismatch-repair-proficient and has low microsatellite instability (pMMR- MSI-L) are focused on.
Journal ArticleDOI

Gut Microbiota and Cancer: From Pathogenesis to Therapy

TL;DR: Novel strategies integrating probiotics, such as LGG, with conventional anti-cancer therapies are strongly encouraged, because of the tight association between gut microbiota and tumorigenesis, as well as Gut microbiota and anti- cancer therapy.
Journal ArticleDOI

‘Final common pathway’ of human cancer immunotherapy: targeting random somatic mutations

TL;DR: Evidence is highlighted suggesting that T cells that target tumor neoantigens arising from cancer mutations are the main mediators of many effective cancer immunotherapies in humans.
Journal ArticleDOI

Difference Between Left-Sided and Right-Sided Colorectal Cancer: A Focused Review of Literature.

TL;DR: Left-sided colorectal cancer (LCRC) patients benefit more from adjuvant chemotherapies such as 5-fluorouracil (5-FU)-based regimes, and targeted therapies such as anti- epidermal growth factor receptor (EGFR) therapy, and have a better prognosis.
References
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Journal ArticleDOI

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TL;DR: Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer.
Journal ArticleDOI

The blockade of immune checkpoints in cancer immunotherapy

TL;DR: Preliminary clinical findings with blockers of additional immune-checkpoint proteins, such as programmed cell death protein 1 (PD1), indicate broad and diverse opportunities to enhance antitumour immunity with the potential to produce durable clinical responses.
Journal ArticleDOI

Signatures of mutational processes in human cancer

Ludmil B. Alexandrov, +84 more
- 22 Aug 2013 - 
TL;DR: It is shown that hypermutation localized to small genomic regions, ‘kataegis’, is found in many cancer types, and this results reveal the diversity of mutational processes underlying the development of cancer.
Journal ArticleDOI

Comprehensive molecular characterization of human colon and rectal cancer

Donna M. Muzny, +320 more
- 19 Jul 2012 - 
TL;DR: Integrative analyses suggest new markers for aggressive colorectal carcinoma and an important role for MYC-directed transcriptional activation and repression.
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Comprehensive molecular characterization of human colon and rectal cancer

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