Immune Checkpoint Blockade for Advanced NSCLC: A New Landscape for Elderly Patients

Perrotta, Fabio; Rocco, Danilo; Vitiello, Fabiana; Palma, Raffaele De; Guerra, Germano; Luca, Antonio De; Navani, Neal; Bianco, Andrea

doi:10.3390/ijms20092258

Cited by 35 publications

(27 citation statements)

References 81 publications

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“…Further evaluations showed that plasma concentrations of IL2, IL7, IL10, GCSF, IP10, MCP1, MIP1A, and TNFα were higher in ICU patients than non-ICU patients [50]. The chaotic increase of excessive cytokines produces a cytokine storm which, along with disruption of anti-inflammatory mechanisms, may prompt an imbalance in coagulative axis resulting in fatal outcomes [51][52][53][54][55][56][57] (Fig. 1).…”

Section: Sars-cov-2 Pathogenesis: Implications For Older Adultsmentioning

confidence: 99%

COVID-19 and the elderly: insights into pathogenesis and clinical decision-making

et al. 2020

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The elderly may represent a specific cluster of high-risk patients for developing COVID-19 with rapidly progressive clinical deterioration. Indeed, in older individuals, immunosenescence and comorbid disorders are more likely to promote viralinduced cytokine storm resulting in life-threatening respiratory failure and multisystemic involvement. Early diagnosis and individualized therapeutic management should be developed for elderly subjects based on personal medical history and polypharmacotherapy. Our review examines the pathogenesis and clinical implications of ageing in COVID-19 patients; finally, we discuss the evidence and controversies in the management in the long-stay residential care homes and aspects of end-of-life care for elderly patients with COVID-19.

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Section: Sars-cov-2 Pathogenesis: Implications For Older Adultsmentioning

confidence: 99%

COVID-19 and the elderly: insights into pathogenesis and clinical decision-making

et al. 2020

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“…Currently, targeted therapies, including those based on the use of EGFR-tyrosine kinase inhibitors (TKIs), BRAF inhibitors, and ALK inhibitors, have demonstrated promising efficacy, with a 60–80% response rate and 9–30 months of progression-free survival in treating advanced NSCLC with relevant driver mutations [ 6 , 8 , 9 ]. Immunotherapy using anti-PD-1/PD-L1 immune checkpoint inhibitors has been developed as a new therapy for metastatic NSCLC that has demonstrated efficacy in numerous clinical trials in which a 15–45% objective response rate was observed in addition to prolonged overall survival [ 7 , 10 , 11 , 12 ]. However, some NSCLC patients still do not have targetable driver mutations and do not benefit from immunotherapy [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

The Crosstalk between Src and Hippo/YAP Signaling Pathways in Non-Small Cell Lung Cancer (NSCLC)

Hsu

Yang

Jablons

et al. 2020

Cancers

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The advancement of new therapies, including targeted therapies and immunotherapies, has improved the survival of non-small-cell lung cancer (NSCLC) patients in the last decade. Some NSCLC patients still do not benefit from therapies or encounter progressive disease during the course of treatment because they have intrinsic resistance, acquired resistance, or lack a targetable driver mutation. More investigations on the molecular biology of NSCLC are needed to find useful biomarkers for current therapies and to develop novel therapeutic strategies. Src is a non-receptor tyrosine kinase protein that interacts with cell surface growth factor receptors and the intracellular signaling pathway to maintain cell survival tumorigenesis in NSCLC. The Yes-associated protein (YAP) is one of the main effectors of the Hippo pathway and has been identified as a promoter of drug resistance, cancer progression, and metastasis in NSCLC. Here, we review studies that have investigated the activation of YAP as mediated by Src kinases and demonstrate that Src regulates YAP through three main mechanisms: (1) direct phosphorylation; (2) the activation of pathways repressing Hippo kinases; and (3) Hippo-independent mechanisms. Further work should focus on the efficacy of Src inhibitors in inhibiting YAP activity in NSCLC. In addition, future efforts toward developing potentially reasonable combinations of therapy targeting the Src–YAP axis using other therapies, including targeted therapies and/or immunotherapies, are warranted.

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“…With age, immune system function is impaired and disrupts the expression of PD-1 and CTLA-4, so the ability to respond to immunotherapy may be altered. Other important age-related changes are: (i) a reduction in CD8 + naïve T cell population; (ii) a stable proportion of CD4 + naïve T cells but with an altered function; (iii) a rise of memory CD4 + T cells and (iv) a higher concentration of inflammatory cytokines [88]. In this context, Kornelis and colleagues studied CD 161 + (C-type lectin receptor) T cells population, which identifies subsets of CD4 + and CD8 + T cells with a strong pro-inflammatory phenotype, in peripheral blood of elderly patients.…”

Section: Discussionmentioning

confidence: 99%

Intratumoral versus Circulating Lymphoid Cells as Predictive Biomarkers in Lung Cancer Patients Treated with Immune Checkpoint Inhibitors: Is the Easiest Path the Best One?

Gascón

Isla

Cruellas

et al. 2020

Cells

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The molecular and cell determinants that modulate immune checkpoint (ICI) efficacy in lung cancer are still not well understood. However, there is a necessity to select those patients that will most benefit from these new treatments. Recent studies suggest the presence and/or the relative balance of specific lymphoid cells in the tumor microenvironment (TEM) including the T cell (activated, memory, and regulatory) and NK cell (CD56dim/bright) subsets, and correlate with a better response to ICI. The analyses of these cell subsets in peripheral blood, as a more accessible and homogeneous sample, might facilitate clinical decisions concerning fast prediction of ICI efficacy. Despite recent studies suggesting that lymphoid circulating cells might correlate with ICI efficacy and toxicity, more analyses and investigation are required to confirm if circulating lymphoid cells are a relevant picture of the lung TME and could be instrumental as ICI response biomarkers. This short review is aimed to discuss the recent advances in this fast-growing field.

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Immune Checkpoint Blockade for Advanced NSCLC: A New Landscape for Elderly Patients

Cited by 35 publications

References 81 publications

COVID-19 and the elderly: insights into pathogenesis and clinical decision-making

COVID-19 and the elderly: insights into pathogenesis and clinical decision-making

The Crosstalk between Src and Hippo/YAP Signaling Pathways in Non-Small Cell Lung Cancer (NSCLC)

Intratumoral versus Circulating Lymphoid Cells as Predictive Biomarkers in Lung Cancer Patients Treated with Immune Checkpoint Inhibitors: Is the Easiest Path the Best One?

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