PD-1 and PD-L1 as immunotherapy targets and biomarkers in non-small cell lung cancer.
PD-1 and PD-L1 as immunotherapy targets and biomarkers in non-small cell lung cancer. J BUON. 2019 May-Jun;24(3):883-888 Authors: Tsoukalas N, Theocharis MKKTMTEAFPBGKS Abstract The integration of immunotherapeutic agents in the treatment of non-small cell lung cancer (NSCLC) has revolutionized the approach of the prevalent type of lung cancer. Although PD-1 and its ligands (PD-L1 and PD-L2) are stimulating molecules of the immune-checkpoint pathway, with primary function to limit inflammatory response and autoimmunity, tumor cells have found a way to exploit these molecules by obtaining the opportunity to respond with PD-L1 expression in cytokine signals and thus to evade immune surveillance. Several immunotherapeutic agents targeting these molecules have already been tested and show quick and remarkable responses and survival prolongation in about 14-20% of chemo-resistant patients in NSCLC, resulting to FDA approval of some PD-1 inhibitors (pebrolizumab, nivolumab), even for first-line treatment of patients with metastatic NSCLC whose tumors have high PD-L1 expression (pebrolizumab). Regarding to the prognostic value of PD-L1 and PD-1 expression as biomarkers in NSCLC, the results still remain contradictory. However, the elevated expression of PD-L1 has been correlated with higher efficacy of the various immunotherapeutic agents, implying a high predictive value of this biomarker, even if the truth about specificity and sensitivity of the aforementione...
Nature Reviews Clinical Oncology, Published online: 20 September 2019; doi:10.1038/s41571-019-0277-2In the past few years, efforts have been made to combine two approaches — immune-checkpoint inhibition and locally ablative radiation therapy — to treat patients with metastatic non-small-cell lung cancer. Herein we discuss the implications of two studies that support the existence of a systemic therapy augmented by radiotherapy (STAR) effect in this setting.
Immunotherapy has been incorporated into the first- and second-line treatment strategies for non-small cell lung cancer (NSCLC), profoundly ushering in a new treatment landscape. However, both adaptive signali...
Immunotherapy with PD-1/PDL-1 checkpoint inhibitors is transforming the landscape in advanced non-small cell lung cancer, prolonging survival to unprecedented lengths compared with chemotherapy alone.Medscape Medical News
CONCLUSIONS: The combination of TMB and CNA can jointly stratify multiple metastatic tumors into groups with different prognosis and heterogenous clinical responses to ICI treatment. Patients with TMBhighCNAlow cancer can be an optimal subgroup for ICI therapy. PMID: 31515453 [PubMed - as supplied by publisher]
ConclusionThis study demonstrates that neoantigen-specific T cells can be detected in peripheral blood in non-small cell lung cancer (NSCLC) patients during anti-PD-L1 therapy. Patients with an objective response had an enrichment of neoantigen-reactive T cells and these cells showed a phenotype that differed from patients without a response. These findings suggest the ex vivo identification, characterization, and longitudinal follow-up of rare tumor-specific differentiated effector neoantigen-specific T cells may be useful in predicting response to checkpoint blockade.Trial registrationPOPLAR trialNCT01903993.
AbstractPatients with non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC) have shown benefit from anti-PD-1 therapies. However, not all patients experience tumor shrinkage, durable responses or prolonged survival, demonstrating the need to find response markers. In blood samples from NSCLC and RCC patients obtained before and after anti-PD-1 treatment, we studied leukocytes by complete blood cell count, lymphocyte subsets using flow cytometry and plasma concentration of nine soluble mediators, in order to find predictive biomarkers of response and to study changes produced after anti-PD-1 therapy. In baseline...
CONCLUSION: Real-world aNSCLC treatment costs are often inconsistent with the NCCN ARs. Given that NCCN Evidence Blocks are intended to inform provider-patient discussions and other decision support resources, such as the NCCN Categories of Preference, our results suggest that the NCCN ARs require further refinement and validation. PMID: 31513478 [PubMed - as supplied by publisher]
ConclusionsAn enhancement of PD-L1 antibody by niclosamide was observed in inhibition of NSCLC growth in vitro and in vivo, which was involved in blockage of p-STAT3 binding to promoter of PD-L1 and finally downregulation of PD-L1 expression. These encourage the combination therapy of niclosamide and PD-1/PD-L1 blockade to be further studied in clinic.
Combination immunotherapy with nivolumab plus ipilimumab was examined as a first-line therapy for patients with advanced non–small-cell lung cancer. Results were presented at the International Associate for the Study of Lung Cancer 2019 World Conference on Lung Cancer.
Non-Small Cell Lung Cancer (NSCLC) is the second most common malignancy worldwide and its incidence increases with age, with about half of the cases diagnosed in people aged ≥70 .