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Tumor Immunotherapy Resistance: Underlying Mechanisms and Emerging Strategies to Overcome Therapeutic Bottlenecks
Review Article  ·  Published: 12 August 2026
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Oncology Communications
Volume 1, Issue 2, 2026: 45-63
Review Article Open Access

Tumor Immunotherapy Resistance: Underlying Mechanisms and Emerging Strategies to Overcome Therapeutic Bottlenecks

by
Ziqing Yuan Ziqing Yuan 1,2
Chenxi Zhou Chenxi Zhou 1,2
Shaoquan Zheng Shaoquan Zheng 1 * ORCID
Jieying Liang Jieying Liang 3 *
1 State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
2 Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510060, China
3 Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Medical Oncology, Sun Yat-sen Memorial Hospital, Guangzhou, China
* Corresponding Authors: Shaoquan Zheng, [email protected]; Jieying Liang, [email protected]
Volume 1, Issue 2
Volume 1, Issue 2 2026
Received: 22 March 2026 Revised: 13 June 2026 Accepted: 20 June 2026 Published: 12 August 2026 CrossMark
Download PDF 1.89 MB Cite Metrics
DOI: 10.62762/OC.2026.289553
ARK: ark:/57805/oc.2026.289553

Article Information

Published in Oncology Communications
Volume/Issue Volume 1, Issue 2, 2026
Pages 45-63

Abstract

This review presents a systematic synthesis of the principal tumor immunotherapy strategies and their corresponding resistance mechanisms. Immunotherapies—including antibody-based therapies, adoptive cell therapies, immune modulators, and novel approaches such as oncolytic viruses and cancer vaccines—work by stimulating or enhancing the patient's immune system to target cancer cells. Nevertheless, they commonly encounter resistance in clinical applications. Resistance mechanisms predominantly stem from tumor-intrinsic factors and tumor microenvironment (TME) factors. To surmount resistance, combination therapies and personalized treatment strategies grounded in TME profiling and biomarkers represent critical future directions.

Graphical Abstract

Tumor Immunotherapy Resistance: Underlying Mechanisms and Emerging Strategies to Overcome Therapeutic Bottlenecks

Keywords

tumor immunotherapy resistance mechanisms tumor microenvironment combination therapy

Data Availability Statement

Not applicable.

Funding

This study was supported by the National Natural Science Foundation of China under Grant 82403987, and by the GuangDong Basic and Applied Basic Research Foundation under Grant 2023A1515111034.

Conflicts of Interest

Shaoquan Zheng served as an Editor-in-Chief, and Jieying Liang served as an Associate Editor of the Oncology Communications at the time of manuscript submission. To ensure the integrity of the peer-review process, neither Shaoquan Zheng nor Jieying Liang was involved in the editorial handling, peer review, or decision-making process for this manuscript, which was handled independently by another editor. The remaining authors declare no conflicts of interest.

AI Use Statement

The authors used AI for language polishing during the preparation of this manuscript.

Ethical Approval and Consent to Participate

Not applicable.

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Yuan, Z., Zhou, C., Liang, J., & Zheng, S. (2026). Tumor Immunotherapy Resistance: Underlying Mechanisms and Emerging Strategies to Overcome Therapeutic Bottlenecks. Oncology Communications, 1(2), 45-64. https://doi.org/10.62762/OC.2026.289553
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TY  - JOUR
AU  - Yuan, Ziqing
AU  - Zhou, Chenxi
AU  - Zheng, Shaoquan
AU  - Liang, Jieying
PY  - 2026
DA  - 2026/08/12
TI  - Tumor Immunotherapy Resistance: Underlying Mechanisms and Emerging Strategies to Overcome Therapeutic Bottlenecks
JO  - Oncology Communications
T2  - Oncology Communications
JF  - Oncology Communications
VL  - 1
IS  - 2
SP  - 45
EP  - 63
DO  - 10.62762/OC.2026.289553
UR  - https://www.icck.org/article/abs/OC.2026.289553
KW  - tumor immunotherapy
KW  - resistance mechanisms
KW  - tumor microenvironment
KW  - combination therapy
AB  - This review presents a systematic synthesis of the principal tumor immunotherapy strategies and their corresponding resistance mechanisms. Immunotherapies—including antibody-based therapies, adoptive cell therapies, immune modulators, and novel approaches such as oncolytic viruses and cancer vaccines—work by stimulating or enhancing the patient's immune system to target cancer cells. Nevertheless, they commonly encounter resistance in clinical applications. Resistance mechanisms predominantly stem from tumor-intrinsic factors and tumor microenvironment (TME) factors. To surmount resistance, combination therapies and personalized treatment strategies grounded in TME profiling and biomarkers represent critical future directions.
SN  - 3142-8894
PB  - Institute of Central Computation and Knowledge
LA  - English
ER  -
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@article{Yuan2026Tumor,
  author = {Ziqing Yuan and Chenxi Zhou and Shaoquan Zheng and Jieying Liang},
  title = {Tumor Immunotherapy Resistance: Underlying Mechanisms and Emerging Strategies to Overcome Therapeutic Bottlenecks},
  journal = {Oncology Communications},
  year = {2026},
  volume = {1},
  number = {2},
  pages = {45-63},
  doi = {10.62762/OC.2026.289553},
  url = {https://www.icck.org/article/abs/OC.2026.289553},
  abstract = {This review presents a systematic synthesis of the principal tumor immunotherapy strategies and their corresponding resistance mechanisms. Immunotherapies—including antibody-based therapies, adoptive cell therapies, immune modulators, and novel approaches such as oncolytic viruses and cancer vaccines—work by stimulating or enhancing the patient's immune system to target cancer cells. Nevertheless, they commonly encounter resistance in clinical applications. Resistance mechanisms predominantly stem from tumor-intrinsic factors and tumor microenvironment (TME) factors. To surmount resistance, combination therapies and personalized treatment strategies grounded in TME profiling and biomarkers represent critical future directions.},
  keywords = {tumor immunotherapy, resistance mechanisms, tumor microenvironment, combination therapy},
  issn = {3142-8894},
  publisher = {Institute of Central Computation and Knowledge}
}

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CC BY Copyright © 2026 by the Author(s). Published by Institute of Central Computation and Knowledge. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/), which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.
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