scholarly journals Case Report: Clinical Management of a Patient With Metastatic Non-Small Cell Lung Cancer Newly Receiving Immune Checkpoint Inhibition During Symptomatic COVID-19

2021 ◽  
Vol 12 ◽  
Author(s):  
Sibylle C. Mellinghoff ◽  
Kanika Vanshylla ◽  
Christine Dahlke ◽  
Marylyn M. Addo ◽  
Oliver A. Cornely ◽  
...  
Keyword(s):  
Lung Cancer ◽  
High Dose ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Underlying Malignancy ◽  
Programmed Death ◽  
Anti Cancer ◽  
Metastatic Lung ◽  
Programmed Death Protein 1 ◽  
Pd1 Blockade

Effects of initiation of programmed-death-protein 1 (PD1) blockade during active SARS-CoV-2 infection on antiviral immunity, COVID-19 course, and underlying malignancy are unclear. We report on the management of a male in his early 40s presenting with highly symptomatic metastatic lung cancer and active COVID-19 pneumonia. After treatment initiation with pembrolizumab, carboplatin, and pemetrexed, the respiratory situation initially worsened and high-dose corticosteroids were initiated due to suspected pneumonitis. After improvement and SARS-CoV-2 clearance, anti-cancer treatment was resumed without pembrolizumab. Immunological analyses with comparison to otherwise healthy SARS-CoV-2-infected ambulatory patients revealed a strong humoral immune response with higher levels of SARS-CoV-2-reactive IgG and neutralizing serum activity. Additionally, sustained increase of Tfh as well as activated CD4+ and CD8+ T cells was observed. Sequential CT scans showed regression of tumor lesions and marked improvement of the pulmonary situation, with no signs of pneumonitis after pembrolizumab re-challenge as maintenance. At the latest follow-up, the patient is ambulatory and in ongoing partial remission on pembrolizumab. In conclusion, anti-PD1 initiation during active COVID-19 pneumonia was feasible and cellular and humoral immune responses to SARS-CoV-2 appeared enhanced in our hospitalized patient. However, distinguishing COVID-19-associated changes from anti-PD1-associated immune-related pneumonitis posed a considerable clinical, radiographic, and immunologic challenge.

scholarly journals Intersection of Sex and Frailty in Humoral Immune Responses to Influenza Vaccine in Community-Dwelling Older Adults

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 271-272
Author(s):  
Janna Shapiro ◽  
Helen Kuo ◽  
Rosemary Morgan ◽  
Huifen Li ◽  
Sabra Klein ◽  
...  
Keyword(s):  
Older Adults ◽  
Immune Responses ◽  
Influenza A ◽  
Community Dwelling ◽  
Influenza Vaccines ◽  
Health Study ◽  
Cardiovascular Health Study ◽  
High Dose ◽  
Humoral Immune ◽  
Humoral Immune Responses

Abstract Older adults bear the highest burden of severe disease and complications associated with seasonal influenza, with annual vaccination serving as the best option for protection. Variability in vaccine efficacy exists, yet the host factors that affect immune responses to inactivated influenza vaccines (IIV) are incompletely understood. We hypothesized that sex and frailty interact to affect vaccine-induced humoral responses among older adults. To test this hypothesis, community-dwelling adults above 75 years of age were recruited yearly, assessed for frailty (as defined by the Cardiovascular Health Study criteria), and vaccinated with the high-dose trivalent IIV. Humoral immune responses were evaluated via hemagglutination inhibition titers. The study began during the 2014-2015 influenza season, with yearly cohorts ranging from 76-163 individuals. A total of 617 vaccinations were delivered from 2014-2019. In preliminary analyses, the outcome of interest was seroconversion, defined as ≥ 4-fold rise in titers. Crude odds ratios suggest that females are more likely to seroconvert to influenza A strains (H1N1: OR = 1.39, (0.98-1.96) ; H3N2: 1.17 (0.85 – 1.62)), while males are more likely to seroconvert to the B strain (OR = 0.85 (0.60 – 1.22)). Furthermore, this sex difference was modified by frailty – for example, the odds of seroconversion to H1N1 were 65% higher for females than males among those who were nonfrail, and only 30% higher among females who were frail. Together, these results suggest that sex and frailty interact to impact immune responses to influenza vaccines. These findings may be leveraged to better protect vulnerable populations.

scholarly journals Deubiquitination and Stabilization of PD-L1 by USP21

2021 ◽  
Author(s):  
Shuying Yang ◽  
Youqian Wu ◽  
Huanhuan Yan ◽  
Bing Shan ◽  
Dongheng Zhou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Squamous Cell Carcinoma ◽  
Mass Spectrometry Analysis ◽  
Polyubiquitin Chains ◽  
Spectrometry Analysis ◽  
Protein Levels ◽  
Programmed Death ◽  
Programmed Death Protein 1 ◽  
Novel Strategy

Abstract Background: The immunotherapy for different types of cancers that targeting programmed death protein-1 (PD-1) and programmed death ligand-1 (PD-L1) has highlighted the importance of suppressing specific T cell responses. Recently, several studies have shown that the expression level of PD-L1 in tumor cells is positively correlated with tumor metastasis as well as recurrence rate. The potent effects of post-translational modifications (PTMs) for PD-L1, such as ubiquitination, glycosylation, phosphorylation and palmitoylation, have been reported to be related to immunosuppression. However, the regulation of PD-L1 degradation in cancers is still not well understood. In this paper, we mainly investigate the deubiquitination regulation of PD-L1. Methods: The protein levels of PD-L1 and USP21 were detected by Immunoblotting and immunohistochemistry. The interaction between PD-L1 and USP21 was determined by co-immunoprecipitation. The deubiquitination of PD-L1 was determined by in vitro deubiquitination assay. The deubiquitination sites of PD-L1 were identified by mass spectrometry analysis. The expression of mRNA in target tissues was presented by bioinformatics analysis.Results: Overexpression of USP21 significantly increased PD-L1 abundance and knockdown of USP21 induced degradation of PD-L1. In vitro deubiquitination assay showed that USP21-WT reduced polyubiquitin chains from PD-L1 while USP21-C221A did not. Furthermore, five lysines in intracellular segment of PD-L1 are potential deubiquitin sites and cancer-derived mutations of PD-L1 in Asp276 have the ability to enhance the deubiquitination of PD-L1 mediated by USP21. Finally, we found that USP21 is the frequently amplified deubiquitinase in lung cancer, especially in lung squamous cell carcinoma, and its amplification co-occurs with the upregulation of PD-L1 levels. Moreover, IHC analysis showed stronger staining of PD-L1 and USP21 in lung cancer samples than adjacent tissues. Conclusion: We identified USP21 as a novel deubiquitinase of PD-L1. Hopefully, targeting PD-L1 by inhibiting USP21 might be a potentially novel strategy for the treatment of lung cancer.

Moderate to high dose cyclophosphamide and intercalated Corynebacterium parvum in patients with metastatic lung cancer

1984 ◽  
Vol 78 ◽  
pp. 89-97 ◽  
Author(s):  
N. Thatcher ◽  
D. Honeybourne ◽  
J. Wagstaff ◽  
K.B. Carroll ◽  
P.V. Barber ◽  
...  
Keyword(s):  
Lung Cancer ◽  
High Dose ◽  
Metastatic Lung Cancer ◽  
Corynebacterium Parvum ◽  
Metastatic Lung

Humoral immune responses of lung cancer patients against tumor antigen NY-ESO-1

2006 ◽  
Vol 236 (1) ◽  
pp. 64-71 ◽  
Author(s):  
Özlem Türeci ◽  
Ulrich Mack ◽  
Ulrich Luxemburger ◽  
Helma Heinen ◽  
Frank Krummenauer ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Immune Responses ◽  
Cancer Patients ◽  
Tumor Antigen ◽  
Lung Cancer Patients ◽  
Humoral Immune ◽  
Humoral Immune Responses

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

2018 ◽  
Vol 12 ◽  
pp. 175346661879413 ◽  
Author(s):  
Nicolas Villanueva ◽  
Lyudmila Bazhenova
Keyword(s):  
Lung Cancer ◽  
Immune System ◽  
Treatment Approach ◽  
Checkpoint Inhibitors ◽  
T Cell Response ◽  
Immune Checkpoints ◽  
Effector T Cell ◽  
Programmed Death ◽  
Programmed Death Protein 1 ◽  
New Strategies

Immunotherapy has significantly altered the treatment landscape for many cancers, including non-small cell lung cancer (NSCLC). Currently approved immuno-oncology agents for lung cancer are aimed at the reversal of immune checkpoints, programmed death protein-1 (PD-1) and programmed death ligand-1 (PD-L1). Although responses to checkpoint inhibitors are encouraging, and in some cases durable, these successes are not universal among all treated patients. In order to optimize our treatment approach utilizing immunotherapy, we must better understand the interaction between cancer and the immune system and evasion mechanisms. In this review, we will provide an overview of the immune system and cancer, and review novel therapies that promote tumor antigen release for immune system detection, activate the effector T-cell response, and reverse inhibitory antitumor signals.

Radiation and Systemic Therapy for Limited-Stage Small-Cell Lung Cancer

2022 ◽  
Author(s):  
Jeffrey A. Bogart ◽  
Saiama N. Waqar ◽  
Michael D. Mix
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Phase Iii ◽  
High Dose ◽  
Small Cell Lung ◽  
Once Daily ◽  
Limited Stage ◽  
Programmed Death

Progress in the overall treatment of small-cell lung cancer (SCLC) has moved at a slower pace than non–small-cell lung cancer. In fact, the standard treatment regimen for limited stage SCLC has not appreciably shifted in more than 20 years, consisting of four to six cycles of cisplatin and etoposide chemotherapy concurrent with thoracic radiotherapy (TRT) followed by prophylactic cranial irradiation (PCI) for responsive disease. Nevertheless, long-term outcomes have improved with median survival approaching 25-30 months, and approximately one third of patients now survive 5 years. This is likely attributable in part to improvements in staging, including use of brain magnetic resonance imaging and fluorodeoxyglucose–positron emission tomography imaging, advances in radiation treatment planning, and supportive care. The CONVERT and CALGB 30610 phase III trials failed to demonstrate a survival advantage for high-dose, once-daily TRT compared with standard 45 Gy twice-daily TRT, although high-dose, once-daily TRT remains common in practice. A phase III comparison of high-dose 60 Gy twice-daily TRT versus 45 Gy twice-daily TRT aims to confirm the provocative outcomes reported with 60 Gy twice daily in the phase II setting. Efforts over time have shifted from intensifying PCI, to attempting to reduce treatment-related neurotoxicity, to more recently questioning whether careful magnetic resonance imaging surveillance may obviate the routine need for PCI. The addition of immunotherapy has resulted in mixed success in extensive-stage SCLC with modest benefit observed with programmed death-ligand 1 inhibitors, and several ongoing trials assess programmed death-ligand 1 inhibition concurrent or adjuvant to chemoradiotherapy in limited-stage SCLC. Major advances in future treatment will likely depend on a better understanding and exploiting of molecular characteristics of SCLC with increasing personalization of therapy.

scholarly journals Intra-tumoral heterogeneity in the expression of programmed-death (PD) ligands in isogeneic primary and metastatic lung cancer: Implications for immunotherapy

2016 ◽  
Vol 5 (9) ◽  
pp. e1213934 ◽  
Author(s):  
David J. Pinato ◽  
Robert J. Shiner ◽  
Solomon D. T. White ◽  
James R. M. Black ◽  
Pritesh Trivedi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Metastatic Lung Cancer ◽  
Programmed Death ◽  
Metastatic Lung

Humoral immune responses of lung cancer patients against the Transmembrane Phosphatase with TEnsin homology (TPTE)

Lung Cancer ◽  
2015 ◽  
Vol 90 (2) ◽  
pp. 334-341 ◽  
Author(s):  
Andreas Kuemmel ◽  
Petra Simon ◽  
Andrea Breitkreuz ◽  
Julia Röhlig ◽  
Ulrich Luxemburger ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Immune Responses ◽  
Cancer Patients ◽  
Lung Cancer Patients ◽  
Humoral Immune ◽  
Humoral Immune Responses

scholarly journals Enhancement of Immune Checkpoint Inhibitor-Mediated Anti-Cancer Immunity by Intranasal Treatment of Ecklonia cava Fucoidan against Metastatic Lung Cancer

2021 ◽  
Vol 22 (17) ◽  
pp. 9125
Author(s):  
Wei Zhang ◽  
Juyoung Hwang ◽  
Dhananjay Yadav ◽  
Eun-Koung An ◽  
Minseok Kwak ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Nk Cells ◽  
Immune Checkpoint ◽  
Intranasal Administration ◽  
Ecklonia Cava ◽  
Metastatic Lung Cancer ◽  
Mucosal Adjuvant ◽  
Cancer Immunity ◽  
Anti Cancer ◽  
Metastatic Lung

Although fucoidan, a well-studied seaweed-extracted polysaccharide, has shown immune stimulatory effects that elicit anticancer immunity, mucosal adjuvant effects via intranasal administration have not been studied. In this study, the effect of Ecklonia cava-extracted fucoidan (ECF) on the induction of anti-cancer immunity in the lung was examined by intranasal administration. In C57BL/6 and BALB/c mice, intranasal administration of ECF promoted the activation of dendritic cells (DCs), natural killer (NK) cells, and T cells in the mediastinal lymph node (mLN). The ECF-induced NK and T cell activation was mediated by DCs. In addition, intranasal injection with ECF enhanced the anti-PD-L1 antibody-mediated anti-cancer activities against B16 melanoma and CT-26 carcinoma tumor growth in the lungs, which were required cytotoxic T lymphocytes and NK cells. Thus, these data demonstrated that ECF functioned as a mucosal adjuvant that enhanced the immunotherapeutic effect of immune checkpoint inhibitors against metastatic lung cancer.

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