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Updated: Jul 2, 2025
Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
Published on: December 9, 2015
Immunotherapy resistance in solid tumors: mechanisms and potential solutions
Daniel S Lefler1, Steven A Manobianco2, Babar Bashir2,3
1Department of Medicine, Division of Hematology and Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Abstract:
While the emergence of immunotherapies has fundamentally altered the management of solid tumors, cancers exploit many complex biological mechanisms that result in resistance to these agents. These encompass a broad range of cellular activities - from modification of traditional paradigms of immunity via antigen presentation and immunoregulation to metabolic modifications and manipulation of the tumor microenvironment. Intervening on these intricate processes may provide clinical benefit in patients with solid tumors by overcoming resistance to immunotherapies, which is why it has become an area of tremendous research interest with practice-changing implications. This review details the major ways cancers avoid both natural immunity and immunotherapies through primary (innate) and secondary (acquired) mechanisms of resistance, and it considers available and emerging therapeutic approaches to overcoming immunotherapy resistance.
Insights
Cancers develop resistance to immunotherapies through complex biological mechanisms affecting immunity and the tumor microenvironment. Understanding these resistance pathways is key to developing new treatments for solid tumors.
Area of Science:
- Oncology
- Immunology
- Cancer Biology
Background:
- Immunotherapies have revolutionized cancer treatment, particularly for solid tumors.
- However, cancer cells develop resistance to these life-saving therapies through diverse biological mechanisms.
- Understanding these resistance mechanisms is crucial for improving patient outcomes.
Purpose of the Study:
- To review the primary (innate) and secondary (acquired) mechanisms by which cancers resist natural immunity and immunotherapies.
- To explore available and emerging therapeutic strategies for overcoming immunotherapy resistance in solid tumors.
Main Methods:
- This review synthesizes current research on cancer resistance to immunotherapy.
- It examines cellular activities including antigen presentation, immunoregulation, metabolic reprogramming, and tumor microenvironment modulation.
Main Results:
- Cancers employ multifaceted strategies to evade immune surveillance and therapeutic interventions.
- Mechanisms of resistance involve alterations in immune signaling, cellular metabolism, and the tumor microenvironment.
- Both innate and acquired resistance pathways contribute to treatment failure.
Conclusions:
- Overcoming immunotherapy resistance in solid tumors requires a comprehensive understanding of cancer's complex evasion tactics.
- Targeting these resistance mechanisms holds significant promise for developing novel, effective cancer therapies.
- Further research into these intricate biological processes is essential for clinical advancement.
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