scholarly journals Frequency of Mismatch Repair Deficiency/High Microsatellite Instability and Its Role as a Predictive Biomarker of response to Immune Checkpoint Inhibitors in Gynecologic Cancers

2021 ◽  
Author(s):  
Joseph J. Noh ◽  
Min Kyu Kim ◽  
Min Chul Choi ◽  
Jeong-Won Lee ◽  
Hyun Park ◽  
...  
Keyword(s):  
Microsatellite Instability ◽  
Mismatch Repair ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Predictive Biomarker ◽  
Mismatch Repair Deficiency ◽  
Gynecologic Cancers ◽  
Repair Deficiency

Immune checkpoint inhibitors for patients with colorectal cancer: mismatch repair deficiency and perspectives

2017 ◽  
Vol 6 (1) ◽  
pp. 23-31
Author(s):  
Romain Cohen ◽  
Magali Svrcek ◽  
Alex Duval ◽  
Yann Parc ◽  
Pia P Österlund ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Mismatch Repair ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Mismatch Repair Deficiency ◽  
Repair Deficiency

scholarly journals Cost-effectiveness of immune checkpoint inhibitors for microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer

Cancer ◽  
2018 ◽  
Vol 125 (2) ◽  
pp. 278-289 ◽  
Author(s):  
Jacqueline N. Chu ◽  
Jin Choi ◽  
Sassan Ostvar ◽  
James A. Torchia ◽  
Kerry Lynn Reynolds ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cost Effectiveness ◽  
Microsatellite Instability ◽  
Metastatic Colorectal Cancer ◽  
Mismatch Repair ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors

Mismatch repair deficiency testing for immune checkpoint therapy: Immunohistochemistry vs microsatellite instability.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. 3022-3022
Author(s):  
Sucha Sudarsanam ◽  
Forrest Blocker ◽  
Sally Agersborg ◽  
Vincent Anthony Funari ◽  
Shiping Jiang ◽  
...  
Keyword(s):  
Microsatellite Instability ◽  
Mismatch Repair ◽  
Immune Checkpoint ◽  
Mismatch Repair Deficiency ◽  
Repair Deficiency

scholarly journals Mismatch Repair Deficiency as a Predictive Biomarker for Immunotherapy Efficacy

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Giulia Viale ◽  
Dario Trapani ◽  
Giuseppe Curigliano
Keyword(s):  
Clinical Trials ◽  
Mismatch Repair ◽  
Checkpoint Inhibitors ◽  
Predictive Biomarkers ◽  
Predictive Biomarker ◽  
Mismatch Repair Deficiency ◽  
Durable Response ◽  
Repair Deficiency ◽  
Cancer Types ◽  
Therapeutic Decision Making

Immunotherapy has revolutionized cancer treatment. Immune-checkpoint inhibitors, on balance, showed a favorable efficacy/toxicity profile with durable response in different cancer types. No predictive biomarker has been validated thus far to select patients who would benefit from therapy. Among the candidate predictive biomarkers, mismatch repair status of the tumor is currently one of the most promising. Indeed, tumors displaying mismatch repair deficiency or microsatellite instability showed remarkable response to immunotherapy in clinical trials. This correlation has been first reported in colorectal cancers, but similar results have been observed also in other cancer types. The possible mechanism behind this correlation may be the higher mutational load observed in mismatch repair deficient tumors, leading to neoantigens formation, recruitment of immune cells, and release of proinflammatory factors in the microenvironment. These results support an approach to treatment based on assessment of the genomic stability of the tumor besides its biologic characteristics and may change our therapeutic decision making process. However, due to the small percentage of patients with tumors displaying mismatch repair deficiency, data from clinical trials should not be considered definitive and need further confirmation.

scholarly journals Current status and perspectives of immune checkpoint inhibitors for colorectal cancer

2020 ◽  
Vol 51 (1) ◽  
pp. 10-19
Author(s):  
Hidekazu Hirano ◽  
Atsuo Takashima ◽  
Tetsuya Hamaguchi ◽  
Dai Shida ◽  
Yukihide Kanemitsu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Metastatic Colorectal Cancer ◽  
Mismatch Repair ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Standard Of Care ◽  
High Level ◽  
Deficient Mismatch Repair

Abstract Immunotherapy, especially immune checkpoint inhibitors, has revolutionized the standard-of-care of multiple types of tumors. For colorectal cancer, the clinical development of immune checkpoint inhibitors is mainly separated according to the status of microsatellite instability or mismatch repair in a tumor. High-level microsatellite instability/deficient mismatch repair metastatic colorectal cancer generally has a tumor microenvironment with infiltration of T cells, associated with a favorable response to immune checkpoint inhibitors. Immune checkpoint inhibitors, including pembrolizumab (anti-PD-1 inhibitor) and nivolumab (anti-PD-1 inhibitor) with or without ipilimumab (anti-CTLA-4 inhibitor), have been integrated into the standard-of-care for high-level microsatellite instability/deficient mismatch repair metastatic colorectal cancer. Conversely, limited T-cell infiltration in the tumor microenvironment of microsatellite stable/proficient mismatch repair metastatic colorectal cancer, which constitutes the majority of metastatic colorectal cancer, is assumed to be a major resistant mechanism to immune checkpoint inhibitors. Currently, clinical trials to improve the clinical activity of immune checkpoint inhibitors by immunomodulation are ongoing for metastatic colorectal cancer. Furthermore, immune checkpoint inhibitors are under development in neoadjuvant and/or adjuvant setting. Here, we review the existing clinical data with ongoing trials and discuss the future perspectives with a focus on the immunotherapy of colorectal cancer.

scholarly journals Tumor Mutational Burden and Mismatch Repair Deficiency Discordance as a Mechanism of Immunotherapy Resistance

2021 ◽  
Vol 19 (2) ◽  
pp. 130-133
Author(s):  
Agata A. Bielska ◽  
Walid K. Chatila ◽  
Henry Walch ◽  
Nikolaus Schultz ◽  
Zsofia K. Stadler ◽  
...  
Keyword(s):  
Lynch Syndrome ◽  
Mismatch Repair ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Cancer Syndrome ◽  
Dna Mismatch ◽  
Mutational Burden ◽  
Repair Deficiency ◽  
Tumor Mutational Burden

Lynch syndrome is a heritable cancer syndrome caused by a heterozygous germline mutation in DNA mismatch repair (MMR) genes. MMR-deficient (dMMR) tumors are particularly sensitive to immune checkpoint inhibitors, an effect attributed to the higher mutation rate in these cancers. However, approximately 15% to 30% of patients with dMMR cancers do not respond to immunotherapy. This report describes 3 patients with Lynch syndrome who each had 2 primary malignancies: 1 with dMMR and a high tumor mutational burden (TMB), and 1 with dMMR but, unexpectedly, a low TMB. Two of these patients received immunotherapy for their TMB-low tumors but experienced no response. We have found that not all Lynch-associated dMMR tumors have a high TMB and propose that tumors with dMMR and TMB discordance may be resistant to immunotherapy. The possibility of dMMR/TMB discordance should be considered, particularly in less-typical Lynch cancers, in which TMB evaluation could guide the use of immune checkpoint inhibitors.

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