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Review
. 2024 Feb 1:15:1352262.
doi: 10.3389/fimmu.2024.1352262. eCollection 2024.

Case report: Efficacy of immunotherapy as conversion therapy in dMMR/MSI-H colorectal cancer: a case series and review of the literature

María San-Román-Gil  1 , Iñigo Martínez-Delfrade  1 , Víctor Albarrán-Fernández  1 , Patricia Guerrero-Serrano  1 , Javier Pozas-Pérez  2 , Jesús Chamorro-Pérez  1 , Diana Rosero-Rodríguez  1 , Pilar Sotoca-Rubio  1 , Ana Maria Barrill-Corpa  1 , Víctor Alia-Navarro  1 , Carlos González-Merino  1 , Coral García-de-Quevedo-Suero  1 , Victoria López  1 , Ignacio Ruz-Caracuel  3 , Cristian Perna-Monroy  3 , Reyes Ferreiro-Monteagudo  1
Affiliations
Review

Case report: Efficacy of immunotherapy as conversion therapy in dMMR/MSI-H colorectal cancer: a case series and review of the literature

María San-Román-Gil et al. Front Immunol. .

Abstract

Immunotherapy has demonstrated a role in the therapeutic landscape of a small subset of patients with colorectal carcinoma (CRC) that harbor a microsatellite instability (MSI-H) status due to a deficient DNA mismatch repair (dMMR) system. The remarkable responses to immune checkpoint inhibitors (ICIs) are now being tested in the neoadjuvant setting in localized CRC, where the dMMR/MSI-H status can be found in up to 15% of patients, with remarkable results obtained in NICHE2 and 3 trials, among others. This case series aims to report our experience at a tertiary center and provide a comprehensive analysis of the possible questions and challenges to overcome if ICIs were established as standard of care in a neoadjuvant setting, as well as the potential role they may have as conversion therapy not only in locoregional advanced CRC but also in oligometastatic disease.

Keywords: colorectal cancer; conversion therapy; immunotherapy; microsatellite instability; neoadjuvant; oligometastatic.

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Conflict of interest statement

RF-M declares the following conflicts of interest—Advisory: Servier, Amgen, Pierre Fabre, Merck Sharp & Dohme (MSD); Speaker: Servier, Amgem, Merck, Pierre Fabre; Travels and other honoraria: Sanofi, Merck, Servier, Amgen. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
1.1. The right colonic mass experienced a considerable decrease in its size from June to August 2021, with no longer evidence of liver or pancreatic infiltration 1.2. (A, B) Transmural full-thickness section of the rectum showing regression changes with no residual neoplasia. Normal mucosa and muscularis propia are coloured green and orange, respectively. The area showing regression changes is coloured in yellow. (C) Some areas of regression showed a mixture of lymphoid and macrophage infiltrates admixed in a collagenous residual stroma. (D) Numerous necrotizing granulomas with a rim of macrophages (>) were present.
Figure 2
Figure 2
A major radiologic response was observed with a clear reduction of the colonic neoplasm and no longer evidence of adjacent suspicious nodes between the basal CT scan and interval CT scan in August 2022. The green arrow represents the absence of lymph node after 5 cycles of pembrolizumab.
Figure 3
Figure 3
3.1 (Case report 3) - The interval CT scan revealed an amelioration of the rectal and adnexal infiltration, with the apparition of a pyometra or a right-annex abscess that provokes an ipsilateral ureterohydronephrosis. A decrease in the abdominopelvic nodes was also observed. 3.2 (Case report 4) - The previously treated with radiofrequency 33-millimetre liver lesion in the right hepatic lobe showed no changes and a remarkable decrease is appreciated in the segment III metastasis, remaining the signs of the hepatic capsule and anterior abdominal wall infiltration. The green arrow indicates the location of the infiltrating liver lesion.
See this image and copyright information in PMC

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