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Neoadjuvant immune checkpoint therapy: Enabling insights into fundamental human immunology and clinical benefit
Kristen E Pauken1, Omar Alhalabi2, Sangeeta Goswami3
1Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Abstract:
While immune checkpoint therapy (ICT) has revolutionized cancer treatment, most patients with advanced disease fail to achieve durable benefit. To address this challenge, it is essential to integrate mechanistic research with clinical studies to: (1) understand response mechanisms, (2) identify patient-specific resistance pathways, (3) develop biomarkers for patient selection, and (4) design novel therapies to overcome resistance. We propose that incorporating "direct-in-patient" studies into clinical trials is crucial for bridging the gap between fundamental science and clinical oncology. In this review, we first highlight recent clinical success of ICT in the neoadjuvant setting, where treatment is given in earlier disease stages to improve outcomes. We then explore how neoadjuvant clinical trials could be utilized to drive mechanistic laboratory-based investigations. Finally, we discuss novel scientific concepts that will potentially aid in overcoming resistance to ICT, which will require future clinical trials to understand their impact on human immune responses.
Insights
Immune checkpoint therapy (ICT) shows promise but often fails in advanced cancers. Integrating mechanistic research with clinical trials, especially in the neoadjuvant setting, is key to understanding resistance and developing effective treatments for better patient outcomes.
Area of Science:
- Oncology
- Immunology
- Translational Medicine
Background:
- Immune checkpoint therapy (ICT) has transformed cancer treatment but benefits are often not durable in advanced disease.
- A significant unmet need exists to overcome resistance to ICT and improve patient outcomes.
Purpose of the Study:
- To review strategies for integrating mechanistic research with clinical studies to enhance ICT efficacy.
- To explore the potential of neoadjuvant clinical trials for driving mechanistic investigations and overcoming resistance.
- To discuss novel therapeutic concepts for improving responses to ICT.
Main Methods:
- Review of recent clinical successes of ICT in the neoadjuvant setting.
- Exploration of how neoadjuvant trials can facilitate mechanistic laboratory research.
- Discussion of scientific concepts for overcoming ICT resistance.
Main Results:
- Neoadjuvant ICT demonstrates clinical success in earlier stages of cancer.
- Neoadjuvant trials offer a platform to investigate ICT response and resistance mechanisms.
Conclusions:
- Integrating mechanistic studies into clinical trials is crucial for advancing ICT.
- Neoadjuvant settings provide unique opportunities to bridge basic science and clinical oncology.
- Future trials are needed to evaluate novel strategies for overcoming ICT resistance.
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