Promising Cellular Immunotherapy for Colorectal Cancer Using Classical Dendritic Cells and Natural Killer T Cells - Review

Sep 23, 2026

Uploaded by Ivy

Colorectal cancer (CRC) remains a major cause of cancer morbidity and mortality worldwide. Despite progress in surgery, chemotherapy, and targeted therapies, metastatic or advanced CRC outcomes are still poor, and checkpoint inhibitor immunotherapies show limited responses. Cellular immunotherapy using classical dendritic cells (cDCs) may improve immune recognition by enabling processing and presentation of tumor antigens. Natural killer T cells are also highlighted as effector cells that connect innate and adaptive responses through crosstalk with dendritic cells. This review evaluates the biological roles, therapeutic strategies, clinical applications, and tumor microenvironment challenges of combining cDCs and NKT cells for synergistic CRC treatment.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages26

Reading Time1 h 6 min

AccessFree to download

Abstract

Keywords

1. Introduction

2. Why Is Colorectal Cancer Difficult to Treat?

2.1. CRC Tumor Heterogeneity and Complex Biology Related to Resistance

Review Promising Cellular Immunotherapy for Colorectal Cancer Using Classical Dendritic Cells and Natural Killer T Cells Mahmoud Singer 1, *, Jennifer Valerin 2, Zhuoli Zhang 1, Zigeng Zhang 1, Farshid Dayyani 2, Vahid Yaghmai 1, April Choi 2, David Imagawa 3 and Nadine Abi-Jaoudeh 1, * Academic Editor: Lluis Espinosa Received: 30 December 2024 Revised: 15 January 2025 Accepted: 20 January 2025 Published: 22 January 2025 Citation: Singer, M.; Valerin, J.; Zhang, Z.; Zhang, Z.; Dayyani, F.; Yaghmai, V.; Choi, A.; Imagawa, D.; Abi-Jaoudeh, N. Promising Cellular Immunotherapy for Colorectal Cancer Using Classical Dendritic Cells and Natural Killer T Cells. Cells 2025, 14, 166. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)cells14030166 Copyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://creativecommons.org/](https://creativecommons.org/)[ ](https://creativecommons.org/)[licenses/by/4.0/](licenses/by/4.0/)) . 1 Department of Radiological Sciences, School of Medicine, University of California, Irvine, CA 92617, USA 2 Department of Medicine, Chao Family Comprehensive Cancer Center, University of California, Irvine, CA 92697, USA; [aprilc@hs.uci.edu](aprilc@hs.uci.edu) (A.C.) 3 Department of Surgery, University of California Irvine, Orange, CA 92697, USA * Correspondence: [singermk@hs.uci.edu](singermk@hs.uci.edu) (M.S.); [nadine@hs.uci.edu](nadine@hs.uci.edu) (N.A.-J.) Abstract: Colorectal cancer (CRC) remains one of the leading causes of cancer-related morbidity and mortality around the world. Despite advances in surgery, chemotherapy, and targeted therapies, the prognosis for patients with metastatic or advanced CRC remains poor. Immunotherapies comprising immune checkpoint inhibitors showed disappointing responses in metastatic CRC (mCRC). However, cellular immunotherapy, specifically using classical dendritic cells (cDCs), may hold unique promise in immune recognition for CRC antigens. cDCs are substantial players in immune recognition and are instrumental in orchestrating innate and adaptive immune responses by processing and presenting tumor antigens to effector cells. Natural killer T (NKT) cells are insufficiently studied but unique effector cells because of their ability to bridge innate and adaptive immune reactions and the crosstalk with dendritic cells in cancer. This review explores the therapeutic potential of using both cDCs and NKT cells as a synergistic therapy in CRC, focusing on their biological roles, strategies for harnessing their capabilities, clinical applications, and the challenges within the tumor microenvironment. Both cDCs and NKT cells can be used as anew effective approach for cell-based therapies in cancers to provide a new hope for CRC patients that are challenging to treat. Keywords: colorectal cancer; CRC; classical dendritic cells; NKT cells; NK cells; tumor microenvironment; TME modulation; cellular immunotherapy 1. Introduction Colorectal cancer (CRC) is the third most commonly diagnosed cancer globally, with an estimated 1.93 million new cases and is the second most common cause of death (0.94 million annually) according to the 2020 worldwide statistics [1–3] . Despite advances in early detection methods and improvements in surgical techniques, chemotherapy, and targeted therapies, metastatic CRC (mCRC) remains challenging to treat, with failure to achieve longterm remission, especially in patients with advanced disease. Hence, mCRC remains a fatal disease with a 5-year survival rate of 14%[4–6] . Novel therapeutic strategies are needed. Immunotherapy has revolutionized cancer treatment, with checkpoint inhibitors and adoptive T cell therapies showing considerable promise in various malignancies [7,8] . However, their application in CRC has been fraught with challenges

FAQs

Why is metastatic or advanced colorectal cancer difficult to treat?

The document links difficulty to complex tumor microenvironment, low tumor mutational burden in microsatellite-stable patients, late-stage diagnosis, treatment resistance, and heterogeneous tumor biology.

What role do classical dendritic cells play in cellular immunotherapy for CRC?

Classical dendritic cells are described as key players in immune recognition that process and present tumor antigens and orchestrate innate and adaptive immune responses.

How do natural killer T cells contribute to a potential synergistic therapy with cDCs?

Natural killer T cells are presented as effector cells that bridge innate and adaptive immunity and interact (crosstalk) with dendritic cells to support anti-tumor reactions.

Sep 23, 2026

Uploaded by Ivy