Immunotherapy is a game-changer in cancer research and treatment. For the first time in decades, its use has led to new standards of care in at least three refractory lung cancers: stage 3 unresectable non-small-cell lung cancer (NSCLC; PACIFIC), extensive-stage small-cell lung cancer (IMpower133), and squamous NSCLC (KEYNOTE-407). Research is rapidly expanding our knowledge of the immune system and how it interacts with cancer cells. While much work remains to be done, progress is accelerating. Future advances will feature new biomarkers and agents as well as new strategic directions, such as "immune normalisation” [1].
Prof. Solange Peters (Lausanne University Hospital and Ludwig Institute, Switzerland) described immunotherapy as a revolution in cancer care. “Over 2000 immunotherapy agents are in development,” she said at the Future of IO, a mini-symposium on immuno-oncology. She showed how phenotypes in the immune cycle are affected by inflamed tumours, lack of T-cells, and immune exclusion—factors that affect the success or failure of immunotherapy.
According to Prof. Peters, it is time to redefine these phenotypes according to immune status, therapeutic aim, and clinical pipeline (see Figure). This approach calls for priming a new response in cold tumours with no effective anti-tumour immunity; potentiating existing responses in cells with suboptimal or exhausted anti-tumour immunity (e.g. PD-L+ tumour); and reversing tumour suppression if immunity is diminished by the tumour microenvironment (e.g. CD73+ tumour). The clinical pipeline offers a wide choice of treatment options for patients in each category, but many are not routinely used in practice.
Figure: Redefined immune cycle, broken out by immune status, therapeutic aim, and clinical pipeline

“The goal is to achieve highly active anti-tumour activity,” said Prof. Peters, who then focused on a self-described list of subjective strategies to focus on. These included TGF-β, a multifunctional cytokine that attenuates tumour response to PD-L1 blockade by contributing to the exclusion of T-cells [2]; ALT-803, an IL-15 superagonist with nivolumab [3]; and NTRK-214, which increases proliferation of tumour-infiltrating lymphocytes and PD-1 expression on the surface of CD8+ T-cells.
She also discussed the targeting of carcinoembryonic antigens in NSCLC and new strategies that specifically exploit the adenosine pathway in NSCLC. “There is incredible room for progress, with some interesting activities of immuno-oncology beyond PD-L1/CTLA-4,” Prof. Peters said. She noted that academic decisions on strategies to prioritise research are critical and warned that drug development is outpacing biological insight. She also lauded participation in clinical trials, noting that it is key to advances in immunotherapy. At the same time, she stressed the importance of patient access to sufficiently established innovation. “That has to be the priority,” she said.
- Sanmamed MF, Chen L. Cell 2018;175:313-326.
- Mariathasan S, et al. Nature 2018;554:544-548.
- Steel JC, et al. Trends Pharmacol Sci 2012;33:35-41.
Posted on
Previous Article
« Small-cell lung cancer circulating tumour cell derived explants Next Article
Letter from the Editor »
« Small-cell lung cancer circulating tumour cell derived explants Next Article
Letter from the Editor »
Table of Contents: WCLC 2018
Featured articles
Interview with the IASCL President, Dr. Giorgio Scagliotti
Presidential Symposium – Top 5 abstracts
Durvalumab after chemoradiotherapy extends OS in stage 3, unresectable non-small-cell lung cancer
Potential for brigatinib as a first-line treatment option for ALK+ non-small-cell lung cancer
Benefits of chest CT screening
New standard of care in extensive-stage small-cell lung cancer
No progression-free survival benefit with nintedanib plus pemetrexed/cisplatin for malignant pleural mesothelioma of epithelial subtype
New Aspects of Immunotherapy
Next generation immunotherapy in non-small-cell lung cancer
Combination therapies: Where are we in 2018?
Choice of taxane and addition of pembrolizumab for metastatic squamous non-small-cell lung cancer
New Aspects of Targeted Therapy
PD-L1 expression in untreated EGFR-mutant non-small-cell lung cancer and response to osimertinib
Mesothelioma
Unmet needs in surgical management of malignant pleural mesothelioma
Advanced Non-small Cell Lung Cancer
Novel Therapies in ROS1 and EGFR
Advances in Small-cell and Neuroendocrine Tumours
Related Articles
November 21, 2018
Entrectinib treatment in patients with ROS1+ NSCLC
November 21, 2018
Combination therapies: Where are we in 2018?
© 2023 Medicom Medical Publishers. All rights reserved. Terms and Conditions | Privacy Policy