Immunotherapy and patients treated for cancer with microsatellite instability

Colle, Raphaël; Cohen, Romain; Cochereau, D.; Duval, Alex; Lascols, Olivier; López-Trabada, Daniel; Afchain, Pauline; Trouilloud, Isabelle; Parc, Yann; Lefèvre, Jérémie H.; Fléjou, Jean‐François; Svrcek, Magali; André, Thierry

doi:10.1016/j.bulcan.2016.11.006

Cited by 72 publications

(51 citation statements)

References 80 publications

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“…In the metastatic setting, dMMR CRCs represent only around 5% and are associated with a poor prognosis [39] , as confirmed in the recent results presented at the 2017 ASCO meeting (OS at 17.9 months and PFS at 3.9 months), whatever the chemotherapy regimen or targeted therapy used (bevacizumab or anti-EGFR) [40] . Actually, immunotherapy is a prominent therapeutic approach in many cancers, such as melanoma, nonsmall cell lung cancer, kidney and bladder cancer.…”

Section: Immunotherapy In Msi Mcrcsupporting

confidence: 50%

Immunotherapy in the treatment of colorectal cancer: a new kid on the block

Spallanzani¹,

Gelsomino²,

Caputo³

et al. 2018

JCMT

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In the last few years, the success of anti-PD1 and anti-PDL1 drugs in solid cancers treatment and the advances in molecular biology have provided new potential treatment strategies for patients with metastatic colorectal cancer. Unfortunately, only patients with mismatch repair deficiency seem to benefit from immunotherapy and they represent a small subset of the metastatic population. New ongoing studies focus on converting an immune ignorant tumour into an inflamed one by combination therapies and on introducing an immunotherapeutic approach in earlier stages of disease (neoadjuvant and adjuvant setting). In this review we summarize the current knowledge about the molecular and immune landscape of colorectal cancer and propose new potential combination strategies to enhance the efficacy of immunotherapy.

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Section: Immunotherapy In Msi Mcrcsupporting

confidence: 50%

Immunotherapy in the treatment of colorectal cancer: a new kid on the block

Spallanzani¹,

Gelsomino²,

Caputo³

et al. 2018

JCMT

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“…Sporadic MSI/MMR-deficient (dMMR) colorectal cancer (CRC), unlike LS-related CRC, is associated with the BRAFV600E mutation, through its association with CIMP (CpG island methylator phenotype) [1]. MMR genes germline mutation cannot always be detected in LS and the definition of sporadic MSI/dMMR CRCs and CRCs presumed to be LS-related (i.e.…”

Section: Introductionmentioning

confidence: 99%

Clinical and molecular characterisation of hereditary and sporadic metastatic colorectal cancers harbouring microsatellite instability/DNA mismatch repair deficiency

Cohen

Buhard

Cervera³

et al. 2017

European Journal of Cancer

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“…Patients with both infiltrating T lymphocytes and PD-L1 expression in the tumor microenvironment most likely will benefit from PD-1/PD-1 blockade [28]. Microsatellite instability (MSI) is also considered a predictive biomarker for response to PD-1/PD-L1 inhibition and, hence, high-level microsatellite-instable cancer patients may be preferred candidates for treatment with checkpoint inhibitors [29]. High-level MSI has been demonstrated in a subset of gastrointestinal NECs, mixed adeno-neuroendocrine carcinoma (MANEC) [30], and sporadic insulinomas [31], but rarely in other GEP-NETs [32,33].…”

Section: Immune Checkpoint Inhibitionmentioning

confidence: 99%

Immune Checkpoint Inhibitors in the Treatment of Patients with Neuroendocrine Neoplasia

Weber

Fottner²

2018

Oncol Res Treat

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Background: Well-differentiated neuroendocrine neoplasms (NENs) are usually controlled by antiproliferative, local ablative and/or radionuclide therapies, whereas poorly differentiated NENs generally require cytotoxic chemotherapy. However, treatment options for patients with advanced/metastatic high-grade NENs remain limited. Method: Review of the literature and international congress abstracts on the efficacy and safety of immunotherapy by checkpoint inhibition in advanced/metastatic NENs. Results: Evidence points to an important role of immune phenomena in the pathogenesis and treatment of neuroendocrine tumors (NETs). Programmed cell death 1 (PD-1) protein and its ligand are mainly expressed in poorly differentiated NENs. Microsatellite instability and high mutational load are more pronounced in high-grade NENs and may predict response to immunotherapy. Clinical experience of immune checkpoint blockade mainly exists for Merkel cell carcinoma, a high-grade cutaneous neuroendocrine carcinoma (NEC), which has led to approval of the anti-PD-1 antibody avelumab. In addition, there is anecdotal evidence for the efficacy of checkpoint inhibitors in large-cell lung NECs, ovarian NECs and others, including gastroenteropancreatic NENs. Currently, phase II studies investigate PDR001, pembrolizumab, combined durvalumab and tremelimumab, and avelumab treatment in patients with advanced/metastatic NENs. Conclusion: Immune checkpoint inhibitors are a promising therapeutic option, especially in progressive NECs or high-grade NETs with high tumor burden, microsatellite instability, and/or mutational load.

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Immunotherapy and patients treated for cancer with microsatellite instability

Cited by 72 publications

References 80 publications

Immunotherapy in the treatment of colorectal cancer: a new kid on the block

Immunotherapy in the treatment of colorectal cancer: a new kid on the block

Clinical and molecular characterisation of hereditary and sporadic metastatic colorectal cancers harbouring microsatellite instability/DNA mismatch repair deficiency

Immune Checkpoint Inhibitors in the Treatment of Patients with Neuroendocrine Neoplasia

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