Potentiating intratumoral therapy with immune checkpoint inhibitors: shifting the paradigm of multimodality therapeutics

Immune checkpoint inhibitors (ICIs) have revolutionized oncology, yielding remarkable and durable responses in various cancers. However, a significant proportion of patients develop resistance to ICIs. The tumor microenvironment plays a critical role in immunotherapy resistance, characterized by imm...

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Main Authors: B.E. Nelson, A. Naing, S. Fu, R.A. Sheth, R. Murthy, S. Piha-Paul
Format: Article
Language:English
Published: Elsevier 2025-03-01
Series:Immuno-Oncology and Technology
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S259001882400337X
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author B.E. Nelson
A. Naing
S. Fu
R.A. Sheth
R. Murthy
S. Piha-Paul
author_facet B.E. Nelson
A. Naing
S. Fu
R.A. Sheth
R. Murthy
S. Piha-Paul
author_sort B.E. Nelson
collection DOAJ
description Immune checkpoint inhibitors (ICIs) have revolutionized oncology, yielding remarkable and durable responses in various cancers. However, a significant proportion of patients develop resistance to ICIs. The tumor microenvironment plays a critical role in immunotherapy resistance, characterized by immune cell composition, regulatory factors, and tumor mutational burden. Intratumoral immunotherapy, involving direct injection of immune-activating agents into tumors, holds promise for converting immunologically ‘cold’ tumors into responsive ‘hot’ tumors. This review explores the rationale for combining intratumoral therapies (ITs) with ICIs, highlighting their complementary mechanisms of action and clinical effects. Notable IT approaches include oncolytic viruses, toll-like receptor agonists, and stimulator of interferon gene agonists with ICIs. Overall, combining ITs with ICIs offers a rational strategy to potentiate antitumor immune response and overcome resistance. Further research is needed to optimize the combination strategies, identify biomarkers of response, and establish the safety and efficacy of these novel therapeutic approaches.
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institution Kabale University
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publishDate 2025-03-01
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series Immuno-Oncology and Technology
spelling doaj-art-0c370c87d3f54a67a0715c2c6910546d2025-02-02T05:29:12ZengElsevierImmuno-Oncology and Technology2590-01882025-03-0125101040Potentiating intratumoral therapy with immune checkpoint inhibitors: shifting the paradigm of multimodality therapeuticsB.E. Nelson0A. Naing1S. Fu2R.A. Sheth3R. Murthy4S. Piha-Paul5Department of Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center, Houston, USADepartment of Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center, Houston, USADepartment of Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center, Houston, USADepartment of Interventional Radiology, University of Texas MD Anderson Cancer Center, Houston, USADepartment of Interventional Radiology, University of Texas MD Anderson Cancer Center, Houston, USADepartment of Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center, Houston, USA; Correspondence to: Prof. Sarina Piha-Paul, Department of Investigational Cancer Therapeutics (A Phase I Clinical Trials Program), Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Tel: +713-563-1055Immune checkpoint inhibitors (ICIs) have revolutionized oncology, yielding remarkable and durable responses in various cancers. However, a significant proportion of patients develop resistance to ICIs. The tumor microenvironment plays a critical role in immunotherapy resistance, characterized by immune cell composition, regulatory factors, and tumor mutational burden. Intratumoral immunotherapy, involving direct injection of immune-activating agents into tumors, holds promise for converting immunologically ‘cold’ tumors into responsive ‘hot’ tumors. This review explores the rationale for combining intratumoral therapies (ITs) with ICIs, highlighting their complementary mechanisms of action and clinical effects. Notable IT approaches include oncolytic viruses, toll-like receptor agonists, and stimulator of interferon gene agonists with ICIs. Overall, combining ITs with ICIs offers a rational strategy to potentiate antitumor immune response and overcome resistance. Further research is needed to optimize the combination strategies, identify biomarkers of response, and establish the safety and efficacy of these novel therapeutic approaches.http://www.sciencedirect.com/science/article/pii/S259001882400337Xintratumoral therapyimmune checkpoint inhibitors
spellingShingle B.E. Nelson
A. Naing
S. Fu
R.A. Sheth
R. Murthy
S. Piha-Paul
Potentiating intratumoral therapy with immune checkpoint inhibitors: shifting the paradigm of multimodality therapeutics
Immuno-Oncology and Technology
intratumoral therapy
immune checkpoint inhibitors
title Potentiating intratumoral therapy with immune checkpoint inhibitors: shifting the paradigm of multimodality therapeutics
title_full Potentiating intratumoral therapy with immune checkpoint inhibitors: shifting the paradigm of multimodality therapeutics
title_fullStr Potentiating intratumoral therapy with immune checkpoint inhibitors: shifting the paradigm of multimodality therapeutics
title_full_unstemmed Potentiating intratumoral therapy with immune checkpoint inhibitors: shifting the paradigm of multimodality therapeutics
title_short Potentiating intratumoral therapy with immune checkpoint inhibitors: shifting the paradigm of multimodality therapeutics
title_sort potentiating intratumoral therapy with immune checkpoint inhibitors shifting the paradigm of multimodality therapeutics
topic intratumoral therapy
immune checkpoint inhibitors
url http://www.sciencedirect.com/science/article/pii/S259001882400337X
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