Impact of mismatch repair deficiency on tumour regression grade after neoadjuvant chemotherapy in localized gastroesophageal adenocarcinoma.

Background: The use of neoadjuvant chemotherapy (NAC) in patients with mismatch repair (MMR) deficient (dMMR) localized gastric and oeso-gastric junction (OGJ) adenocarcinoma is subject of debate. Histological response assessment might help to better evaluate the impact of dMMR on response to NAC.

Methods: Patients with localized gastric/OGJ adenocarcinoma resected after NAC were retrospectively identified.

Immune Checkpoint Inhibition in Metastatic Colorectal Cancer Harboring Microsatellite Instability or Mismatch Repair Deficiency.

Microsatellite instability (MSI) is a tumor phenotype related to a deficient DNA mismatch repair system (dMMR). This phenotype, observed in 5% of metastatic mCRC but 10-18% of localized CRC, is associated with high tumor mutational burden with highly immunogenic neoantigens. It has emerged as a major predictive biomarker for the efficacy of ICIs.

[Going beyond microsatellite instability for immunotherapy in metastatic colorectal cancer: Consensus molecular subtypes and tumor mutational burden].

Next generation immunotherapies have limited efficacy in colorectal cancer. Immune checkpoints inhibitors demonstrated their benefit in mismatch repair-deficient tumors, which also exhibit microsatellite instability (MSI). The Consensual Molecular Subtype (CMS) classification has been recently proposed and highlights specific immune escape mechanisms for each subtype.