Immunotherapy for Advanced Non–Small Cell Lung Cancer: A Decade of Progress

Shields, Morgan C.; Marin-Acevedo, Julian A.; Pellini, Bruna

doi:10.1200/edbk_321483

Cited by 84 publications

(69 citation statements)

References 37 publications

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“…The idea to utilize the patients’ immune system to fight tumors has revolutionized the field of anticancer therapy within the last decade [ 9 ]. In fact, immunotherapeutic approaches have been triumphant in several highly immunogenic cancers, often called “hot tumors” (such as melanoma, renal carcinoma, and lung cancer, among others) [ 10 , 11 , 12 ]. Thus, immune-checkpoint monotherapies or combination regimens targeting cytotoxic T lymphocyte antigen 4 (CTLA-4) and/or the programmed death-1 (PD-1)/PD-1 ligand (PD-L1) axis have become an integral part of various first-line standard therapies in a variety of malignancies.…”

Section: Introductionmentioning

confidence: 99%

Immunotherapy in Advanced Prostate Cancer—Light at the End of the Tunnel?

Amsberg

Alsdorf

Karagiannis

et al. 2022

IJMS

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Immunotherapeutic treatment approaches are now an integral part of the treatment of many solid tumors. However, attempts to integrate immunotherapy into the treatment of prostate cancer have been disappointing so far. This is due to a highly immunosuppressive, “cold” tumor microenvironment, which is characterized, for example, by the absence of cytotoxic T cells, an increased number of myeloid-derived suppressor cells or regulatory T cells, a decreased number of tumor antigens, or a defect in antigen presentation. The consequence is a reduced efficacy of many established immunotherapeutic treatments such as checkpoint inhibitors. However, a growing understanding of the underlying mechanisms of tumor–immune system interactions raises hopes that immunotherapeutic strategies can be optimized in the future. The aim of this review is to provide an overview of the current status and future directions of immunotherapy development in prostate cancer. Background information on immune response and tumor microenvironment will help to better understand current therapeutic strategies under preclinical and clinical development.

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Section: Introductionmentioning

confidence: 99%

Immunotherapy in Advanced Prostate Cancer—Light at the End of the Tunnel?

Amsberg

Alsdorf

Karagiannis

et al. 2022

IJMS

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“…Almost half of NSCLC patients show no EGFR mutation (EGFR WT) (Xu et al, 2015), leaving chemotherapy and immunotherapy as the only viable therapeutic options (Tomasini et al, 2017). Clinical trials have demonstrated anti-PD-1/anti-PD-L1 therapies can prolong overall survival in EGFR WT NSCLC patients (To et al, 2021), and chemotherapy combined with immunotherapy was approved by the United States FDA in 2020 for the treatment of metastatic or recurrent NSCLC (Shields et al, 2021). Nevertheless, the utility of these therapies is limited by adverse effects of anti-PD-1/anti-PD-L1 treatments (Su et al, 2020) and the high prices for immunotherapeutic drugs (Green, 2021).…”

Section: Introductionmentioning

confidence: 99%

Hedgehog Suppresses Paclitaxel Sensitivity by Regulating Akt-Mediated Phosphorylation of Bax in EGFR Wild-Type Non-Small Cell Lung Cancer Cells

Yeh

et al. 2022

Front. Pharmacol.

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Non-small cell lung cancer (NSCLC) is one of the most common and deadly cancers worldwide. Among NSCLC patients, almost half have wild-type epidermal growth factor receptor (EGFR WT). The primary therapeutic option for these EGFR WT NSCLC patients is chemotherapy, while NSCLC patients with EGFR mutations have more diverse therapeutic options, including EGFR tyrosine kinase inhibitors. Moreover, NSCLC patients with EGFR WT have worse chemotherapy response than EGFR mutant NSCLC patients. Thus, an urgent need exists for novel therapeutic strategies to improve chemotherapy response in EGFR WT NSCLC patients. Hedgehog signaling is known to be highly active in NSCLC; however, its potential role in chemoresistance is not fully understood. In the present study, we found that paclitaxel (PTX) treatment induces hedgehog signaling in EGFR WT NSCLC cells, and inhibition of hedgehog signaling with GDC-0449 (Vismodegib) increases sensitivity to PTX-stimulated apoptosis. Furthermore, GDC-0449 potentiates PTX-induced reactive oxygen species and mitochondrial dysfunction. In contrast, a hedgehog agonist, Hh-Ag1.5, attenuates PTX-induced apoptosis. Mechanistic experiments revealed that hedgehog induces phosphorylation of Akt at Ser473. Akt then phosphorylates Bax at Ser184, which can switch its activity from pro-apoptosis to anti-apoptosis. Taken together, our findings suggest that inhibition of hedgehog signaling might be a promising therapeutic strategy to improve PTX response in EGFR WT NSCLC.

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“…Over the last decade, different types of drugs, including targeted therapy and immunotherapy, have become available, resulting in a shift in the treatment paradigm for patients with NSCLC. 2 Immune checkpoint inhibitors (ICIs) bind to the programmed death 1 (PD‐1) receptor or programmed death ligand 1 (PD‐L1) and allow activated T cells to induce tumor cell death by blocking the binding of the PD‐1 ligand of tumor cells to the PD‐1 receptor of immune cells. 3 , 4 , 5 , 6 In recent years, immunotherapy has become the standard of care for NSCLC.…”

Section: Introductionmentioning

confidence: 99%

The rest period between chemotherapy and immunotherapy influences the efficacy of immune checkpoint inhibitors in lung cancer

et al. 2022

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Background The use of immune checkpoint inhibitors (ICIs) as first‐line treatment rather than as second‐line treatment makes a big difference in the drug efficacy and progression‐free survival. However, the mechanism for this is still not clear. This study aimed to analyze the effects of the rest period between chemotherapy and immunotherapy on the efficacy of ICIs. Methods This study included 100 patients with advanced NSCLC treated with PD‐1/PD‐L1 inhibitors at Chungnam National University Hospital (CNUH) between May 2016 and August 2019. The rest period was defined from the last dose of cytotoxic chemotherapy to the first dose of ICIs. We retrospectively reviewed patients' clinical data and blood test records and analyzed lymphocyte subsets using flow cytometry. Results The median rest period was 64 days. The long rest period group (≥36 days) showed significantly higher clinical benefits than the short rest period group (<36 days) (69.4% vs. 39.5%, p = 0.003). White blood cell (WBC) count, absolute neutrophil count (ANC), absolute lymphocyte count (ALC), and neutrophil‐lymphocyte ratio (NLR) just before chemotherapy were not different between the two groups. However, the blood test after chemotherapy immediately before immunotherapy showed significantly higher ANC and NLR in the short rest period group than in the long rest period group. The frequency of the Th1 subset and PD‐1 + CD8 + T cells were significantly higher in the long rest period group than in the short rest period group. Conclusion Time interval from chemotherapy to immunotherapy may affect immune cell status and efficacy of ICIs.

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Immunotherapy for Advanced Non–Small Cell Lung Cancer: A Decade of Progress

Cited by 84 publications

References 37 publications

Immunotherapy in Advanced Prostate Cancer—Light at the End of the Tunnel?

Immunotherapy in Advanced Prostate Cancer—Light at the End of the Tunnel?

Hedgehog Suppresses Paclitaxel Sensitivity by Regulating Akt-Mediated Phosphorylation of Bax in EGFR Wild-Type Non-Small Cell Lung Cancer Cells

The rest period between chemotherapy and immunotherapy influences the efficacy of immune checkpoint inhibitors in lung cancer

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