Immune evasion in cancer - mechanisms and cutting-edge therapeutic approaches

Sep 23, 2026

Immune evasion represents a major obstacle in oncology by enabling tumors to escape immune surveillance and destruction, which undermines therapeutic effectiveness and worsens patient outcomes. This review consolidates how cancers avoid immune detection through tumor-induced immune suppression, immune checkpoint regulation, and genetic and epigenetic influences. It also examines the tumor microenvironment’s contribution to immune resistance, metabolic reprogramming, and tumor heterogeneity, alongside the limitations of current immunotherapies and the roles of key signaling pathways.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages49

Reading Time2 h 3 min

AccessFree to download

Introduction

Mechanisms of immune evasion in cancer

Tumor-induced immune suppression

Signal Transduction [and Targeted Therapy](and Targeted Therapy www.nature.com/sigtrans)[ www.nature.com/sigtrans](and Targeted Therapy www.nature.com/sigtrans) REVIEW ARTICLE OPEN Immune evasion in cancer: mechanisms and cutting-edge therapeutic approaches Muhammad Tufail 1, Can-Hua Jiang1,2,3,4 and Ning Li1,2,3,4 ✉ | | Immune evasion represents a signiﬁcant challenge in oncology. It allows tumors to evade immune surveillance and destruction, thereby complicating therapeutic interventions and contributing to suboptimal patient outcomes. This review addresses the critical need to understand how cancers evade immune surveillance. It aims to provide a comprehensive overview of strategies of tumors to escape immune detection by examining tumor-induced immune suppression, immune checkpoint regulation, and genetic and epigenetic inﬂuences. Moreover, it explores the dynamic role of the tumor microenvironment (TME) in fostering immune resistance and highlights the impact of metabolic reprogramming on immune suppression. Additionally, this review focuses on how tumor heterogeneity inﬂuences immune evasion and discusses the limitations of current immunotherapies. The role of key signaling pathways, including programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1), cytotoxic Tlymphocyte–associated antigen 4 (CTLA-4), transforming growth factor-β (TGF-β), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS–STING) is analyzed to elucidate their contributions to immune escape. Emphasizing the complexities of immune evasion, this review underscores the importance of personalized approaches and the integration of multi-omics data to combat therapeutic resistance. Furthermore, it discusses novel and emerging therapeutic strategies, such as bispeciﬁc antibodies, oncolytic viruses, and nanotechnology-driven immunotherapies, showcasing innovative avenues in cancer treatment. The signiﬁcance of this review lies in its potential to guide future research and | | | --- | --- | --- | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | innovations in immunotherapy, ultimately improving patient outcomes and advancing our understanding of cancer immunology. | | | | | Signal Transduction and Targeted Therapy (2025)10:227 ; [https://doi.org/10.1038/s41392-025-02280-1](https://doi.org/10.1038/s41392-025-02280-1) | | | | | | INTRODUCTION Cancer remains a signiﬁcant challenge for modern medicine.1 The immune system is essential for recognizing and destroying abnormal cells, maintaining cellular homeostasis, and protecting against malignant changes.2 However, cancer cells are using various complex mechanisms to evade immune surveillance, enabling them to grow uncontrollably and ultimately form lifethreatening tumors.3,4 The immune evasion phenomenon in cancer involves a complex interplay among tumor cells, the TME, and immune cells.5 Tumor cells evade immune detection and destruction through various strategies, including altering antigen presentation, creating an immunosuppressive microenvironment, and inhibiting immune cell function.6,7 These tactics enable cancer cells to persist and grow despite the immune system’s efforts to eradicate them. Recent immunology and oncology advances reveal mechanisms of immune evasion, providing new insights into how cancer cells manage to subvert immune responses.8,9 New ﬁndings have led to treatments targeting immune evasion, including immune checkpoint inhibitors (ICIs), CAR-T cell therapy, and cancer vaccines, offering hope for previously untreatable cancers.10, 11 This review article provides a complete summary of how cancer cells escape the immune system and the most recent breakthroughs in therapy to address these obstacles. We will look at the essential signaling pathways involved in immune eva

FAQs

Why is immune evasion in cancer a significant clinical challenge?

It allows tumors to evade immune surveillance and destruction, complicating therapeutic interventions and contributing to suboptimal patient outcomes.

What strategies do tumors use to escape immune detection?

Tumors can alter antigen presentation, create immunosuppressive tumor microenvironments, inhibit immune cell function, and use checkpoint molecules that blunt immune responses.

Which emerging therapies and signaling pathways are discussed in the review?

The review covers strategies such as bispecific antibodies, oncolytic viruses, and nanotechnology-driven immunotherapies, and analyzes pathways including PD-1/PD-L1, CTLA-4, TGF-β, NF-κB, and cGAS–STING.

Sep 23, 2026

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