Clinical status and future prospects of neoadjuvant immunotherapy for localized mismatch repair-deﬁcient cancers - a review

Sep 21, 2026

Uploaded by Theodore

Frameshift mutations accumulate in cancers with mismatch repair deficiency (dMMR), enabling the production of diverse neoantigens and defining a subset of tumors with strong immunotherapy responsiveness. Evidence has expanded from first-line treatment of metastatic dMMR cancers to earlier, up-front strategies including neoadjuvant therapy. Completed small trials suggest high complete response rates, but clinicians must balance good established care for proficient MMR against limited follow-up data for neoadjuvant immunotherapy.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages11

Reading Time28 min

AccessFree to download

Introduction

Rationale for neoadjuvant immunotherapy in localized dMMR cancers

Biomarkers and clinical challenges

Highlights and clinical status

Evidence from clinical trials

Safety, response, and resistance considerations

Biological rationale and future directions

Issues for advancing the field

’Review Article Clinical status and future prospects of neoadjuvant immunotherapy for localized mismatch repairdeﬁcient cancers: a review Jian Li, MMed* Abstract Frameshift mutations accumulate in cancers related to mismatch repair deﬁciency (dMMR), which has the potential to produce various neoantigens, representing a distinct subset of cancers that respond considerably to immunotherapy. In recent years, robust evidence has supported the ﬁrst-line application of immunotherapy for patients with metastatic dMMR cancers, which provoked extensive investigations of the feasibility and efﬁcacy of immunotherapy in up-front settings, including neoadjuvant therapy. Several completed trials with small sample sizes suggested that neoadjuvant immunotherapy can achieve an impressively high complete response rate, for the ﬁrst time offering the potential of systemic therapy to cure cancer without the need for surgical resection. However, a difﬁcult dilemma emerges: clinicians are now facing a selection between the standard of care with good evidence for proﬁcient MMR but suboptimal for dMMR cancers and the emerging immunotherapy with promising results but only based on a limited number of patients with shorter duration of follow-up. This review aims to provide a comprehensive summary of the biological rationale and clinical status of neoadjuvant immunotherapy in patients with dMMR cancers. Furthermore, I elaborate on particular issues that must be taken into consideration for further advancement in the ﬁeld. Keywords: immune checkpoint inhibitors, localized cancer, microsatellite instability, mismatch repair deﬁciency, neoadjuvant immunotherapy, nonoperative management Introduction Immunotherapy has revolutionized the treatment paradigm for advanced-stage cancers, providing an unprecedented survival beneﬁtin selected patients[1,2] . However, only a minority of patients are expected to respond to immunotherapy[3] . Therefore, the application of neoadjuvant immunotherapy in localized cancers has attracted much attention in recent years, aiming to activate more solid anticancer immunity against existing neoantigens. In both localized and metastatic settings, an issue impeding the successful application of immunotherapy is the lack of perfect biomarkers for stratifying patients, as not every patient responds equally. Therefore, identifying reliable biomarkers to select patients who are likely to beneﬁt from immunotherapy has attracted much attention Department of General Surgery, The Third Hospital of Mianyang, Sichuan Mental Health Center, Mianyang, Sichuan, People ’s Republic of China Sponsorships or competing interests that maybe relevant to content are disclosed atthe end of this article. *Corresponding author. Address: Department of General Surgery, The Third Hospital of Mianyang, No. 190 East Section of Jiannan Road, Youxian District, Sichuan 621000, People ’s Republic of China. Tel.: +86 133 308 939 77. [E-mail: 654747973@qq.com](E-mail: 654747973@qq.com) (J. Li). Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. International Journal of Surgery (2024) 110:5722–5732 Received 27 March 2024; Accepted 9 May 2024 Published online 20 May 2024 [http://dx.doi.org/10.1097/JS9.0000000000001680](http://dx.doi.org/10.1097/JS9.0000000000001680) HIGHLIGHTS • In the past several years, several clinical trials on neoadjuvant immunotherapy for mismatch repair-deﬁcient (dMMR) cancer have been published, offering systemic therapy to cure solid cancer without surgery for the ﬁrst time. • The comprehensive literature review of neoadjuvant immunotherapy for dMMR cancer is lacking, while this treatment paradigm may be a hot topic and will change the standard of therapy for lo

FAQs

Why are dMMR cancers considered suitable for immunotherapy?

dMMR drives microsatellite instability and accumulation of frameshift mutations, which can generate many neoantigens and supports immunotherapy responsiveness.

What progress has been reported for neoadjuvant immunotherapy in localized dMMR cancers?

Several small completed trials indicate neoadjuvant immunotherapy can produce impressively high complete response rates with relatively low severe adverse effects.

What dilemma complicates choosing neoadjuvant immunotherapy for localized dMMR cancers?

Clinicians must weigh established standard-of-care for proficient MMR against emerging immunotherapy results for dMMR, which are based on limited patients and shorter follow-up.

Sep 21, 2026

Uploaded by Theodore