ESMO recommendations on microsatellite instability testing for immunotherapy in cancer, and its relationship with PD-1/PD-L1 expression and tumour mutational burden: a systematic review-based…

By C. Luchini, F. Bibeau, M. Ligtenberg, Naveena Singh, A. Nottegar, T. Bosse, R. Miller, N. Riaz, J. Douillard, F. André and 1 more. Annals of Oncology, 2019

896 citations recorded by the source corpus.

BACKGROUND Cancers with a defective DNA mismatch repair (dMMR) system contain thousands of mutations most frequently located in monomorphic microsatellites and are thereby defined as having microsatellite instability (MSI). Therefore, MSI is a marker of dMMR. MSI/dMMR can be identified using immunohistochemistry to detect loss of MMR proteins and/or molecular tests to show microsatellite alterations. Together with tumour mutational burden (TMB) and PD-1/PD-L1 expression, it plays a role as a predictive biomarker for immunotherapy. METHODS To define best practices to implement the detection of dMMR tumours in clinical practice, the ESMO Translational Research and Precision Medicine Working Group launched a collaborative project, based on a systematic review-approach, to generate consensus recommendations on the: (i) definitions related to the concept of MSI/dMMR; (ii) methods of MSI/dMMR testing and (iii) relationships between MSI, TMB and PD-1/PD-L1 expression. RESULTS The MSI-related definitions, for which a consensus frame-work was used to establish definitions, included: 'microsatellites', 'MSI', 'DNA mismatch repair' and 'features of MSI tumour'. This consensus also provides recommendations on MSI testing; immunohistochemistry for the mismatch repair proteins MLH1, MSH2, MSH6 and PMS2 represents the first action to assess MSI/dMMR (consensus with strong agreement); the second method of MSI/dMMR testing is represented by polymerase chain reaction (PCR)-based assessment of microsatellite alterations using five microsatellite markers including at least BAT-25 and BAT-26 (strong agreement). Next-generation sequencing, coupling MSI and TMB analysis, may represent a decisive tool for selecting patients for immunotherapy, for common or rare cancers not belonging to the spectrum of Lynch syndrome (very strong agreement). The relationships between MSI, TMB and PD-1/PD-L1 expression are complex, and differ according to tumour types. CONCLUSIONS This ESMO initiative is a response to the urgent questions raised by the growing success of immunotherapy and provides also important insights on the relationships between MSI, TMB and PD-1/PD-L1.

Subfields: Epidemiology, Oncology, Pathology and Forensic Medicine

View Paper: https://www.semanticscholar.org/paper/2691b9d9ef60f2d7a6357ff2bf3fd870cb0da0a5

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Citations in the corpus

Clinical-grade Detection of Microsatellite Instability in Colorectal Tumors by Deep Learning. (2020, neutral): “Jakob Nikolas Kather(1),(3), (11),(16)”
Immune Checkpoint Inhibitors in Cancer Therapy (2022, background): “Microsatellite unstable tumours have been categorized into two phenotypes namely MSI-low (MSI-L) and MSI-high (MSI-H) that the latter enhanced significantly the neoantigen load, leading to activating lymphocyte, thereby rendering tumour cells sensitive to ICIs [116].”
Intratumoral and peritumoral radiomics of MRIs predicts pathologic complete response to neoadjuvant chemoimmunotherapy in patients with head and neck squamous cell carcinoma (2024, unknown): “15 16 Radiomics is a rapidly evolving technique to transform medical images into high-throughput and quantifiable data.”