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Immunotherapy for Lung Malignancies: From Gene Sequencing to Novel Therapies
Jonathan Chee1, Bruce W S Robinson2, Robert A Holt3
1National Centre of Asbestos Related Diseases, School of Medicine and Pharmacology, University of Western Australia; Perth, Western Australia, Australia.
Abstract:
Harnessing the immune system to fight cancer is an exciting advancement in lung cancer therapy. Antitumor immunity can be augmented by checkpoint blockade therapy, which removes the inhibition/brakes imposed on the immune system by the tumor. Checkpoint blockade therapy with anti-programmed cell death protein 1 (anti-PD-1)/anti-programmed death ligand 1 (anti-PDL-1) antibodies causes tumor regression in about 25% of patients with lung cancer. In another approach, the immune system is forced or accelerated to attack the tumor through augmentation of the antitumor response against mutations carried by each lung tumor. This latter approach has become feasible since the advent of next-generation sequencing technology, which allows identification of the specific mutations that each individual lung tumor bears. Indeed lung cancers are now known to have high mutation rates, making them logical targets for mutation-directed immune therapies. We review how sequencing of lung cancer mutations leads to better understanding of how the immune system recognizes tumors, providing improved opportunities to track antitumor immunity and ultimately leading to the development of personalized vaccine strategies aimed at unleashing the host immune system to attack mutations in the tumor.
Insights
Harnessing the immune system through checkpoint blockade or mutation-directed therapies offers new lung cancer treatment options. Sequencing lung tumors aids in developing personalized vaccines to boost antitumor immunity.
Area of Science:
- Oncology
- Immunology
- Genomics
Background:
- Cancer immunotherapy, particularly checkpoint blockade (anti-PD-1/anti-PDL-1), shows promise in lung cancer, yielding tumor regression in approximately 25% of patients.
- Lung tumors possess high mutation rates, making them susceptible to immune attack when these mutations are identified.
Purpose of the Study:
- To review advancements in harnessing the immune system for lung cancer therapy.
- To explore how sequencing lung cancer mutations improves understanding of tumor recognition and facilitates personalized vaccine development.
Main Methods:
- Review of current research on immune checkpoint blockade therapy for lung cancer.
- Discussion of next-generation sequencing's role in identifying tumor-specific mutations.
- Analysis of how mutation identification enhances understanding of antitumor immunity.
Main Results:
- Checkpoint blockade therapy (anti-PD-1/anti-PDL-1) achieves tumor regression in a subset of lung cancer patients.
- Next-generation sequencing enables the identification of specific mutations in individual lung tumors.
- Understanding tumor mutations improves tracking of antitumor immunity and development of personalized vaccines.
Conclusions:
- Personalized vaccine strategies targeting tumor mutations can enhance the host immune system's attack on lung cancer.
- Sequencing lung cancer mutations is crucial for developing effective, tailored immunotherapies.
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