Neoadjuvant immunotherapy based on PD-1/L1 inhibitors for gastrointestinal tumors: a review of the rationale and clinical advances - review

Sep 21, 2026

Upload by Violet

The landscape of tumor treatment has been transformed by immunotherapy targeting PD-1/PD-L1. By mobilizing systemic antitumor immunity mainly mediated by T cells, interest has grown in applying this approach across multiple stages of cancer care. Neoadjuvant immunotherapy aims to generate a strong immune response before surgery, reducing tumor burden, suppressing tumor cell activity, limiting metastatic spread, improving curative resection rates, and preventing recurrence. The review summarizes preclinical rationale, clinical challenges, and progress for gastrointestinal tumors, while noting limited high-quality randomized trials and the need to define regimens, patient selection, and measurable endpoints.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages16

Reading Time40 min

AccessFree to download

Abstract

Introduction

Rationale for neoadjuvant therapy

Limitations of conventional neoadjuvant therapy

PD-1/PD-L1 inhibitors and immune checkpoint activation

HIGHLIGHTS

Summary of preclinical evidence

Summary of clinical trial advancements

Gaps and future research needs

’Review article Neoadjuvant immunotherapy based on PD-1/L1 inhibitors for gastrointestinal tumors: a review of the rationale and clinical advances Dong-Xu Wang, PhD, MD, Hui Liu, MD, Jin-Cheng Tian, MSc, Dao-Lin Zhang, BSc, Lun-Jie Yan, MD, Zi-Niu Ding, MD, Han Li, MSc, Yu-Chuan Yan, PhD, MD, Zhao-Ru Dong, PhD, MD, Tao Li, PhD, MD Abstract The landscape of current tumor treatment has been revolutionized by the advent of immunotherapy based on PD-1/PD-L1 inhibitors. Leveraging its capacity to mobilize systemic antitumor immunity, which is primarily mediated by T cells, there is growing exploration and expansion of its potential value in various stages of clinical tumor treatment. Neoadjuvant immunotherapy induces a robust immune response against tumors prior to surgery, effectively facilitating tumor volume reduction, early eradication or suppression of tumor cell activity, and control of potential metastatic spread, to improve curative surgical resection rates, and prevent tumor recurrence. This review delineates the theoretical basis of neoadjuvant immunotherapy from preclinical research evidence, discusses speciﬁc challenges in clinical application, and provides a comprehensive overview of clinical research progress in neoadjuvant immunotherapy for gastrointestinal tumors. These ﬁndings suggest that neoadjuvant immunotherapy has the potential to ameliorate immunosuppressive states and enhance cytotoxic T cell function while preserving lymphatic drainage in the preoperative period. However, further investigations are needed on speciﬁc treatment regimens, suitable patient populations, and measurable endpoints. Despite numerous studies demonstrating the promising efﬁcacy and manageable adverse events of neoadjuvant immunotherapy in gastrointestinal tumors, the availability of high-quality randomized controlled trials is limited, which highlights the necessity for further research. Keywords: gastrointestinal tumor, neoadjuvant immunotherapy, PD-1/L1 inhibitors, tumor microenvironment Introduction Neoadjuvant therapy is a comprehensive tumor treatment modality involving the administration of radiation, chemotherapy, targeted agents, or their combination prior to curative surgery that improves patient survival and is recommended for the treatment of various cancers, such as breast, esophageal, colorectal, and prostate cancer[1,2]. However, conventional neoadjuvant therapy primarily Department of General Surgery, Qilu Hospital, Shandong University, Jinan, People’s Republic of China Dong-Xu Wang, Hui Liu, Jin-Cheng Tian, and Dao-LinZhang are equal contributors. Sponsorships or competing interests that maybe relevant to content are disclosed atthe end of this article. *Corresponding author. Address: Department of General Surgery, Qilu Hospital, Shandong University, 107 West Wen Hua Road, Jinan 250012, People ’s Republic of China. Tel.: +86 531 821 666 51. E-mail: [litao7706@163.com](litao7706@163.com) (T. Li). Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. This is an open access article distributed under the Creative Commons AttributionNoDerivatives License 4.0, which allows for redistribution, commercial and noncommercial, as long as it is passed along unchanged and in whole, with credit to the author. International Journal of Surgery (2024) 110:3707–3722 Received 25 October 2023; Accepted 3 March 2024 Supplemental Digital Content is available for this article. Direct URL citations are provided in the HTML and PDF versions of this article on the journal's website, [www.lww.com/international-journal-of-surgery](www.lww.com/international-journal-of-surgery). Published online 21 March 2024 [http://dx.doi.org/10.1097/JS9.0000000000001357](http://dx.doi.org/10.1097/JS9.0000000000001357) HIGHLIGHTS • This study extensively summarizes the current preclinical evidence that has been conﬁrmed within the ﬁeld of neoadjuvant immunotherapy. • Latest advancements in clinical trial

FAQs

What is the purpose of neoadjuvant immunotherapy in gastrointestinal tumors?

It is designed to induce a robust immune response before surgery, helping reduce tumor volume, eradicate or suppress tumor cell activity early, control potential metastatic spread, and improve curative resection rates while preventing recurrence.

How do PD-1/PD-L1 inhibitors differ from conventional neoadjuvant treatments?

Conventional approaches rely on cytotoxic drugs or physical interventions that can disrupt the immune system and create immunosuppressive microenvironments. PD-1/PD-L1 targeted immune checkpoint inhibitors aim to activate host immunity and harness cytotoxic T cells for tumor recognition and eradication while minimizing damage to normal cells.

What key research gaps are highlighted in the review?

Despite promising efficacy and manageable adverse events, the availability of high-quality randomized controlled trials is limited. Further studies are needed to determine specific treatment regimens, suitable patient populations, and measurable endpoints, and to evaluate other immune checkpoint targets in the neoadjuvant setting.

Sep 21, 2026

Upload by Violet