New strategies in immunotherapy for lung cancer: beyond PD-1/PD-L1

Villanueva, Nicolas; Bazhenova, Lyudmila

doi:10.1177/1753466618794133

Cited by 37 publications

(39 citation statements)

References 219 publications

(283 reference statements)

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“…. Three main scenarios for further investigations are release of cancer antigens (vaccination, adoptive cell therapy), activation of the T-cell response (TNF-R superfamily), and regulation of the inhibitory immune response (Ig superfamily, metabolites and myeloid cell factors) (86) with a lot of interesting new drugs (87). Among them, we may cite IDO inhibitors as epacadostat, although the first results were disappointing.…”

Section: Perspectivesmentioning

confidence: 99%

Immunotherapy: From Advanced NSCLC to Early Stages, an Evolving Concept

et al. 2020

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Immunotherapy in lung cancer treatment is a long history paved with failures and some successes. During the last decade, the discovery of checkpoints inhibitors led to major advances in treating advanced and metastatic non-small cell lung cancer (NSCLC). Impressive data from early phase I-II studies were subsequently confirmed in large prospective randomized trials and meta-analyses (High-level of evidence). Three anti-programmed death-1 (PD1) (pembrolizumab, nivolumab) or antiPD-ligand(L)1 (atezolizumab) antibodies showed clinically significant improved survival compared to second-line docetaxel. Then, first-line pembrolizumab monotherapy demonstrated its superiority over platinum-doublet in high PD-L1 NSCLC. The addition of pembrolizumab or atezolizumab to chemotherapy derived the same results regardless of the PD-L1 status. On the opposite, antiCTLA4 (Cytotoxic T-Lymphocyte Associated 4) results are currently disappointing in unselected patients while recent development suggest that the combination of antiPD1 and antiCTLA4 (nivolumab-ipilimumab) positively impact on overall survival. Some secondary analyses also showed that immunotherapy has a positive impact on quality of life and that the clinical improvement can be done at an acceptable incremental cost per QALY. A lot of questions remain unresolved: which is the best treatment duration and is it the same for all patients, how to choose the patients that will have the highest benefit of immunotherapy, how to identify the patients who will have rapid progression, how to improve the current data (new targets, new combinations)…

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Section: Perspectivesmentioning

confidence: 99%

Immunotherapy: From Advanced NSCLC to Early Stages, an Evolving Concept

et al. 2020

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“…Interestingly, targeting the CD39/CD73/ADORA axis may have non-redundant functions, in that co-targeting CD73 and the A2A receptor improves the efficacy of either inhibitor alone [103], though this study was not completed in the context of improving the efficacy of currently FDA-approved immunotherapy antibodies such as those that block PD(L)1. This preclinical work has culminated in the initiation of clinical trials which combine each of these agents with PD-1/PD-L1 blocking antibodies [104,105] (ClinicalTrials.gov identifiers: NCT02503774, NCT03549000, NCT03454451, NCT02403193, NCT02655822, NCT03207867). Similar to these efforts to target the canonical pathway via CD39/CD73 inhibitors, data generated from our laboratory reveal similar efficacy may be achieved by targeting CD38.…”

Section: Targeting Adenosine-generating Pathwaysmentioning

confidence: 99%

The Good, the Bad and the Unknown of CD38 in the Metabolic Microenvironment and Immune Cell Functionality of Solid Tumors

Konen

Fradette

Gibbons

2019

Cells

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The regulation of the immune microenvironment within solid tumors has received increasing attention with the development and clinical success of immune checkpoint blockade therapies, such as those that target the PD-1/PD-L1 axis. The metabolic microenvironment within solid tumors has proven to be an important regulator of both the natural suppression of immune cell functionality and the de novo or acquired resistance to immunotherapy. Enzymatic proteins that generate immunosuppressive metabolites like adenosine are thus attractive targets to couple with immunotherapies to improve clinical efficacy. CD38 is one such enzyme. While the role of CD38 in hematological malignancies has been extensively studied, the impact of CD38 expression within solid tumors is largely unknown, though most current data indicate an immunosuppressive role for CD38. However, CD38 is far from a simple enzyme, and there are several remaining questions that require further study. To effectively treat solid tumors, we must learn as much about this multifaceted protein as possible—i.e., which infiltrating immune cell types express CD38 for functional activities, the most effective CD38 inhibitor(s) to employ, and the influence of other similarly functioning enzymes that may also contribute towards an immunosuppressive microenvironment. Gathering knowledge such as this will allow for intelligent targeting of CD38, the reinvigoration of immune functionality and, ultimately, tumor elimination.

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“…Immune escape mechanism is one of the reasons why tumor cells can continuously replicate and proliferate in the human body . Programmed cell death‐1/programmed cell death ligand‐1 (PD‐1/PD‐L1) inhibitors developed by selectively blocking the pathway involved in tumor cell escape have spring boarded this therapy to a new stage, which to a certain extent may maintain longer‐lasting antitumor effects . We suggest that for lung cancer patients receiving immunotherapy during the epidemic, it is not urgent to receive immunotherapy on a set date.…”

Section: Recommendations Of Individualized Medical Treatment Strategiesmentioning

confidence: 99%

Recommendations of individualized medical treatment and common adverse events management for lung cancer patients during the outbreak of COVID‐19 epidemic

et al. 2020

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Since its outbreak in December 2019 in China, the novel coronavirus disease has rapidly spread and affected several countries. It has resulted in a difficult situation for cancer patients owing to the risks of the epidemic situation outbreak as well as cancer. Patients with cancer are more likely than the general population to contract COVID-19 because of the systemic immunosuppressive status caused by malignant diseases or anticancer treatment. Lung cancer has the highest morbidity and mortality in China and the world. Most patients with lung cancer are smokers with poor underlying lung conditions and low immunity, thus it is vital to protect them from epidemic diseases during cancer treatment. It is necessary to provide individualized medical treatment and management of treatment-related adverse events for patients with lung cancer based on patients' conditions and regional epidemic patterns. Key pointsSignificant findings of the study During the outbreak of COVID-19, taking patients' conditions and regional epidemic patterns into consideration, providing appropriate individualized treatment strategies for lung cancer patients with different stages is an urgent requirement. What this study adds Based on the characteristics of lung cancer, this article aims to provide recommendations and suggestions of individualized treatment strategies and management of common adverse events for patients with lung cancer during the epidemic period of COVID-19.

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New strategies in immunotherapy for lung cancer: beyond PD-1/PD-L1

Cited by 37 publications

References 219 publications

Immunotherapy: From Advanced NSCLC to Early Stages, an Evolving Concept

Immunotherapy: From Advanced NSCLC to Early Stages, an Evolving Concept

The Good, the Bad and the Unknown of CD38 in the Metabolic Microenvironment and Immune Cell Functionality of Solid Tumors

Recommendations of individualized medical treatment and common adverse events management for lung cancer patients during the outbreak of COVID‐19 epidemic

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