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Resistance to immunotherapy in human malignancies: Mechanisms, research progresses, challenges, and opportunities
Davood Bashash1, Zahra Zandi2, Bahareh Kashani2
1Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Abstract:
Despite remarkable advances in different types of cancer therapies, an effective therapeutic strategy is still a major and significant challenge. One of the most promising approaches in this regard is immunotherapy, which takes advantage of the patients' immune system; however, the many mechanisms that cancerous cells harbor to extend their survival make it impossible to gain perfect eradication of tumors. The response rate to cancer immunotherapies, especially checkpoint inhibitors and adoptive T cell therapy, substantially differs in various cancer types with the highest rates in advanced melanoma and non-small cell lung cancer. Indeed, the lack of response in many tumors indicates primary resistance that can originate from either tumor cells (intrinsic) or tumor microenvironment (extrinsic). On the other hand, some tumors show an initial response to immunotherapy followed by relapse in few months (acquired resistance). Understanding the underlying molecular mechanisms of immunotherapy resistance makes it possible to develop effective strategies to overcome this hurdle and boost therapy outcomes. In this review, we take a look at immunotherapy strategies and go through a number of primary and acquired resistance mechanisms. Also, we present various ongoing methods to overcoming resistance and introduce some promising fields to improve the outcome of immunotherapy in patients affected with cancer.
Insights
Cancer immunotherapy shows promise but faces resistance. Understanding and overcoming intrinsic and extrinsic resistance mechanisms is key to improving treatment outcomes for various cancer types.
Area of Science:
- Oncology
- Immunology
- Cancer Research
Background:
- Cancer immunotherapy leverages the patient's immune system for treatment.
- Significant challenges remain in achieving complete tumor eradication due to cancer cell survival mechanisms.
- Response rates to immunotherapies like checkpoint inhibitors and adoptive T cell therapy vary significantly across cancer types, with higher efficacy in melanoma and non-small cell lung cancer.
Purpose of the Study:
- To review current cancer immunotherapy strategies.
- To elucidate primary (intrinsic/extrinsic) and acquired resistance mechanisms.
- To present methods for overcoming resistance and improving patient outcomes.
Main Methods:
- Literature review of immunotherapy strategies.
- Analysis of molecular mechanisms underlying immunotherapy resistance.
- Exploration of current and emerging strategies to overcome resistance.
Main Results:
- Immunotherapy response rates differ across cancer types, with notable success in advanced melanoma and non-small cell lung cancer.
- Primary resistance can stem from tumor cells or the tumor microenvironment.
- Acquired resistance leads to relapse after initial response.
Conclusions:
- Understanding immunotherapy resistance mechanisms is crucial for developing effective therapeutic strategies.
- Overcoming resistance through novel approaches holds promise for enhancing cancer treatment outcomes.
- Further research into promising fields is needed to improve immunotherapy efficacy in cancer patients.
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