---
title: "Oncolytic Viruses plus Immune Checkpoint Inhibitors to Overcome Melanoma Drug Resistance"
id: "pubmed-42757474"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42757474"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42757474/"
doi: "10.3892/or.2026.9197"
published_at: "2026-09-18T12:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Oncolytic Viruses plus Immune Checkpoint Inhibitors to Overcome Melanoma Drug Resistance
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42757474
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42757474/)
- **DOI:** [10.3892/or.2026.9197](https://doi.org/10.3892%2For.2026.9197)
- **Published At:** 2026-09-18T12:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- Advanced melanoma increasingly benefits from **immune checkpoint inhibitors** (ICIs), but approximately half of patients develop primary or acquired resistance and fail to derive meaningful clinical benefit. - The expanding use of ICIs in adjuvant and neoadjuvant settings increases the number of patients with ICI‑resistant disease, creating an urgent clinical need for effective salvage therapies. - Patients whose melanoma progresses after combined **PD‑1** and **CTLA‑4** blockade have limited effective treatment options; novel strategies are required. - **Oncolytic viruses** (OVs) offer dual antitumor mechanisms: selective tumor cell lysis and immunomodulatory remodeling of the **tumor immune microenvironment**, making them attractive partners for ICIs. - Recent preclinical and clinical advances have translated OV–ICI combinations from conceptual strategies into clinically evaluable regimens for refractory melanoma. - Key translational barriers remain: interpatient heterogeneity in response, unclear optimal sequencing and dosing for combinations, and absence of validated predictive biomarkers. - The review synthesizes emerging clinical evidence and mechanistic insights into OV–ICI synergy to guide rational trial design, refine combination strategies, and support development of precision immuno‑oncology approaches for melanoma. - The article emphasizes the need for translational research to address heterogeneity, optimize combination parameters, and identify biomarkers to broaden clinical implementation of OV–ICI therapy.
## Clinical Analysis & Structured Key Points
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Epub 2026 Sep 18. # Overcoming melanoma drug resistance: Mechanisms and clinical progress of oncolytic viruses combined with immune checkpoint inhibitors (Review) [Yuan He](https://pubmed.ncbi.nlm.nih.gov/?term=He+Y&cauthor_id=42757474)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42757474/#full-view-affiliation-1 "School of Integrated Traditional Chinese and Western Medicine, Gansu University of Chinese Medicine, Lanzhou, Gansu 730000, P.R. China."), [Wenxuan Lin](https://pubmed.ncbi.nlm.nih.gov/?term=Lin+W&cauthor_id=42757474)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42757474/#full-view-affiliation-1 "School of Integrated Traditional Chinese and Western Medicine, Gansu University of Chinese Medicine, Lanzhou, Gansu 730000, P.R. China."), [Haofang Chen](https://pubmed.ncbi.nlm.nih.gov/?term=Chen+H&cauthor_id=42757474)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42757474/#full-view-affiliation-2 "Department of Integrated Traditional Chinese and Western Medicine, Gansu Hospital Affiliated to Sun Yat‑sen University Cancer Center, Lanzhou, Gansu 730050, P.R. China."), [Yongqi Guan](https://pubmed.ncbi.nlm.nih.gov/?term=Guan+Y&cauthor_id=42757474)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42757474/#full-view-affiliation-1 "School of Integrated Traditional Chinese and Western Medicine, Gansu University of Chinese Medicine, Lanzhou, Gansu 730000, P.R. China."), [Congcong Guan](https://pubmed.ncbi.nlm.nih.gov/?term=Guan+C&cauthor_id=42757474)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42757474/#full-view-affiliation-1 "School of Integrated Traditional Chinese and Western Medicine, Gansu University of Chinese Medicine, Lanzhou, Gansu 730000, P.R. China."), [Yanxiang Zhang](https://pubmed.ncbi.nlm.nih.gov/?term=Zhang+Y&cauthor_id=42757474)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42757474/#full-view-affiliation-1 "School of Integrated Traditional Chinese and Western Medicine, Gansu University of Chinese Medicine, Lanzhou, Gansu 730000, P.R. China."), [Dongsheng Pan](https://pubmed.ncbi.nlm.nih.gov/?term=Pan+D&cauthor_id=42757474)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42757474/#full-view-affiliation-3 "Gansu Provincial Hospital of Traditional Chinese Medicine, Lanzhou, Gansu 730000, P.R. China.") Affiliations Expand ### Affiliations * 1 School of Integrated Traditional Chinese and Western Medicine, Gansu University of Chinese Medicine, Lanzhou, Gansu 730000, P.R. China. * 2 Department of Integrated Traditional Chinese and Western Medicine, Gansu Hospital Affiliated to Sun Yat‑sen University Cancer Center, Lanzhou, Gansu 730050, P.R. China. * 3 Gansu Provincial Hospital of Traditional Chinese Medicine, Lanzhou, Gansu 730000, P.R. China. * PMID: **42757474** * DOI: [ 10.3892/or.2026.9197 ](https://doi.org/10.3892/or.2026.9197) Item in Clipboard Review # Overcoming melanoma drug resistance: Mechanisms and clinical progress of oncolytic viruses combined with immune checkpoint inhibitors (Review) Yuan He et al. Oncol Rep. 2026 Nov. Show details Display options Display options Format Abstract PubMed PMID Oncol Rep Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Oncol+Rep%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Oncol+Rep%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42757474/) . 2026 Nov;56(5):191. doi: 10.3892/or.2026.9197. Epub 2026 Sep 18. ### Authors [Yuan He](https://pubmed.ncbi.nlm.nih.gov/?term=He+Y&cauthor_id=42757474)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42757474/#short-view-affiliation-1 "School of Integrated Traditional Chinese and Western Medicine, Gansu University of Chinese Medicine, Lanzhou, Gansu 730000, P.R. China."), [Wenxuan Lin](https://pubmed.ncbi.nlm.nih.gov/?term=Lin+W&cauthor_id=42757474)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42757474/#short-view-affiliation-1 "School of Integrated Traditional Chinese and Western Medicine, Gansu University of Chinese Medicine, Lanzhou, Gansu 730000, P.R. China."), [Haofang Chen](https://pubmed.ncbi.nlm.nih.gov/?term=Chen+H&cauthor_id=42757474)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42757474/#short-view-affiliation-2 "Department of Integrated Traditional Chinese and Western Medicine, Gansu Hospital Affiliated to Sun Yat‑sen University Cancer Center, Lanzhou, Gansu 730050, P.R. China."), [Yongqi Guan](https://pubmed.ncbi.nlm.nih.gov/?term=Guan+Y&cauthor_id=42757474)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42757474/#short-view-affiliation-1 "School of Integrated Traditional Chinese and Western Medicine, Gansu University of Chinese Medicine, Lanzhou, Gansu 730000, P.R. China."), [Congcong Guan](https://pubmed.ncbi.nlm.nih.gov/?term=Guan+C&cauthor_id=42757474)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42757474/#short-view-affiliation-1 "School of Integrated Traditional Chinese and Western Medicine, Gansu University of Chinese Medicine, Lanzhou, Gansu 730000, P.R. China."), [Yanxiang Zhang](https://pubmed.ncbi.nlm.nih.gov/?term=Zhang+Y&cauthor_id=42757474)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42757474/#short-view-affiliation-1 "School of Integrated Traditional Chinese and Western Medicine, Gansu University of Chinese Medicine, Lanzhou, Gansu 730000, P.R. China."), [Dongsheng Pan](https://pubmed.ncbi.nlm.nih.gov/?term=Pan+D&cauthor_id=42757474)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42757474/#short-view-affiliation-3 "Gansu Provincial Hospital of Traditional Chinese Medicine, Lanzhou, Gansu 730000, P.R. China.") ### Affiliations * 1 School of Integrated Traditional Chinese and Western Medicine, Gansu University of Chinese Medicine, Lanzhou, Gansu 730000, P.R. China. * 2 Department of Integrated Traditional Chinese and Western Medicine, Gansu Hospital Affiliated to Sun Yat‑sen University Cancer Center, Lanzhou, Gansu 730050, P.R. China. * 3 Gansu Provincial Hospital of Traditional Chinese Medicine, Lanzhou, Gansu 730000, P.R. China. * PMID: **42757474** * DOI: [ 10.3892/or.2026.9197 ](https://doi.org/10.3892/or.2026.9197) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID ## Abstract Although immune checkpoint inhibitors (ICIs) have revolutionized the management of advanced melanoma, a major clinical challenge persists: Nearly 50% of patients develop primary or acquired resistance and therefore derive no meaningful clinical benefit. As ICIs are increasingly used in earlier disease settings, including adjuvant and neoadjuvant therapy, the population of patients with ICI‑resistant disease continues to grow. For patients whose disease progresses after first‑line combined programmed cell death 1 (PD‑1) and cytotoxic T‑lymphocyte associated protein 4 (CTLA‑4) blockade, effective salvage options remain limited, highlighting an urgent unmet medical need. Oncolytic viruses (OVs), which exert antitumor effects through the dual mechanisms of selective tumor cell lysis and immunomodulatory remodeling of the tumor microenvironment, represent a compelling therapeutic strategy for overcoming ICI resistance. Recent clinical and preclinical advances have moved OV‑ICI combination regimens from conceptual strategies to clinically evaluable interventions for refractory melanoma. Nevertheless, several translational barriers impede their broader implementation, including interpatient heterogeneity in treatment response, uncertainty regarding the optimal sequencing and dosing of combination therapies, and the lack of validated predictive biomarkers. The present review systematically synthesizes emerging clinical evidence and mechanistic insights into OV‑ICI synergy to inform rational trial design, refine combination strategies, and accelerate the development of precision immuno‑oncology approaches. **Keywords:** immune checkpoint inhibitors; immune resistance; melanoma; oncolytic viruses; tumor immune microenvironment. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Similar articles * [ Synergy of oncolytic adenovirus and immune checkpoint inhibitors: transforming cancer immunotherapy paradigms. ](https://pubmed.ncbi.nlm.nih.gov/40698086/) Cheng C, Wang Q, Zhang S.Cheng C, et al.Front Immunol. 2025 Jul 8;16:1610858. doi: 10.3389/fimmu.2025.1610858. eCollection 2025.Front Immunol. 2025.PMID: 40698086Free PMC article.Review. * [ Immune Checkpoint Inhibitors Combined with Oncolytic Virotherapy: Synergy, Heterogeneity, and Safety in Cancer Treatment. ](https://pubmed.ncbi.nlm.nih.gov/41425703/) Feng Y, Yang H, Liang G, Chen J, Li T, Wang Y, Chang J, Li Y, Yang M, Zhou X, Wang Z, Ge C.Feng Y, et al.Oncol Res. 2025 Nov 27;33(12):3801-3836. doi: 10.32604/or.2025.067824. eCollection 2025.Oncol Res. 2025.PMID: 41425703Free PMC article.Review. * [ Combination of oncolytic Maraba virus with immune checkpoint blockade overcomes therapy resistance in an immunologically cold model of advanced melanoma with dysfunctional T-cell receptor signalling. ](https://pubmed.ncbi.nlm.nih.gov/39060020/) Armstrong E, Chiu MKL, Foo S, Appleton L, Nenclares P, Patrikeev A, Mohan N, Mclaughlin M, Bozhanova G, Hoebart J, Roulstone V, Patin E, Pedersen M, Kyula J, Ono M, Errington-Mais F, Bell J, Harrington KJ, Melcher A, Jennings V.Armstrong E, et al.J Immunother Cancer. 2024 Jul 25;12(7):e009443. doi: 10.1136/jitc-2024-009443.J Immunother Cancer. 2024.PMID: 39060020Free PMC article. * [ Oncolytic viruses: advanced strategies in cancer therapy. ](https://pubmed.ncbi.nlm.nih.gov/41639062/) Xiao D, Zhang H, Liu Y, Li Y, Li G, Ning Y.Xiao D, et al.Signal Transduct Target Ther. 2026 Feb 5;11(1):45. doi: 10.1038/s41392-025-02343-3.Signal Transduct Target Ther. 2026.PMID: 41639062Free PMC article.Review. * [ The Challenge of Treating Anti-PD-1-Resistant Advanced Melanoma. ](https://pubmed.ncbi.nlm.nih.gov/40670749/) Vestergaard CD, Ellebaek E, Borch TH, Donia M, Svane IM.Vestergaard CD, et al.Am J Clin Dermatol. 2025 Sep;26(5):777-794. doi: 10.1007/s40257-025-00969-1. Epub 2025 Jul 17.Am J Clin Dermatol. 2025.PMID: 40670749Review. 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