Combination Immunotherapy in Non-small Cell Lung Cancer

Marmarelis, Melina E.; Aggarwal, Charu

doi:10.1007/s11912-018-0697-7

Cited by 28 publications

(26 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Recent evidence demonstrates that B7-H3-expressing NSCLC escapes antitumor immunity via CD8 + T-cell repression despite anti-PD-1 immunotherapy and that B7-H3 blockade, especially in combination with the PD-1 blockade, exhibits potent antitumor efficacy mediated by increased number of tumor-specific CD8 + T cells [ 22 ]. This study represented a novel and promising therapeutic strategy against B7-H3-expressing tumors [ 22 , 23 , 24 , 25 , 26 , 27 , 28 ].…”

Section: Discussionmentioning

confidence: 99%

“…B7-H3 (CD276) belongs to a family of immune modulators that also includes PD-L1 (also known as B7-H1) [ 19 , 20 , 21 ]. Recent evidence demonstrates that B7-H3 blockade, especially when combined with an anti-PD-1 blockade, is a promising strategy for the treatment of B7-H3-expressing NSCLCs that are refractory to anti-PD-1 therapy [ 22 ], making B7-H3 a promising molecular target [ 22 , 23 , 24 , 25 , 26 , 27 , 28 ]. However, the association of B7-H3 expression with survival in patients with pancreatic cancer remains elusive.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Tumor B7-H3 (CD276) Expression and Survival in Pancreatic Cancer

Inamura

Takazawa

Inoue

et al. 2018

JCM

View full text Add to dashboard Cite

B7-H3 (CD276), a member of the family of immune modulators, orchestrates antitumor immunity. To date, only small-sized studies have examined the association of B7-H3 expression with survival in pancreatic cancer, yielding inconclusive results. We evaluated tumor B7-H3 expression in 150 consecutive patients with pancreatic ductal adenocarcinoma using immunohistochemistry. B7-H3 expression was positive (≥10% tumor cells) in 99 of 150 (66%) cases of pancreatic cancer. We classified the tumors into four groups depending on B7-H3 expression (negative, low, intermediate, and high) and found that higher B7-H3 expression was independently associated with lower disease-free survival (DFS; for high vs. negative B7-H3 expression: multivariable hazard ratio (HR) = 3.12; 95% confidence interval (CI) = 1.48–6.15; Ptrend = 0.0026). Furthermore, the association of B7-H3 expression with survival differed according to the pathological stage (p-stage) (Pinteraction = 0.048, between p-stages I–II and III–IV). The association of B7-H3 positivity with lower DFS was stronger in tumors with p-stage I–II (multivariable HR = 3.10, 95% CI = 1.75–5.69; P < 0.0001) than in those with p-stage III–IV (multivariable HR = 1.20, 95% CI = 0.67–2.28; P = 0.55). We demonstrated that tumor high B7-H3 expression is independently associated with poor survival in patients with pancreatic cancer and that this association is stronger in tumors with p-stage I–II than in those with p-stage III–IV. B7-H3 expression may be a useful prognostic biomarker for identifying aggressive early-stage pancreatic cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Tumor B7-H3 (CD276) Expression and Survival in Pancreatic Cancer

Inamura

Takazawa

Inoue

et al. 2018

JCM

View full text Add to dashboard Cite

show abstract

“…It has been demonstrated that angiogenic factors are immunosuppressive, implying that a combination of immune checkpoint blockade with antiangiogenic agents may exhibit synergistic antitumor activity in NSCLC treatments. Indeed, primary data from clinical trials in combination therapy with immune checkpoint blockade (nivolumab and pembrolizumab) and antiangiogenic agents (bevacizumab, ramucirumab, and nintedanib) show promising results for NSCLC [ 60 ]. For example, the phase I trial ( NCT01454102 ) evaluated the efficacy and safety of combination maintenance treatment of nivolumab with bevacizumab in advanced NSCLC patients with response to first-line platinum-based chemotherapy.…”

Section: Anti-pd-1/pd-l1-based Combinatory Therapies For Nsclc Trementioning

confidence: 99%

Anti-PD-1/PD-L1 Therapy for Non-Small-Cell Lung Cancer: Toward Personalized Medicine and Combination Strategies

Sui

Wang

et al. 2018

Journal of Immunology Research

162

139

View full text Add to dashboard Cite

Lung cancer remains a leading cause of cancer-related mortality worldwide with the poor prognosis. Encouragingly, immune checkpoint blockade targeting programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) has dramatically changed the landscape for treatments in patients with non-small-cell lung cancer (NSCLC). However, only a small proportion of NSCLC patients responded to monotherapy of anti-PD-1/PDL1 agents; together, the development of resistance to anti-PD-1/PD-L1 therapy that leads to failure of anti-PD-1/PD-L1 therapy has significantly limited a broad applicability of the findings in clinical practices. Nowadays, several companion diagnostic assays for PDL1 expression have been introduced for identifying patients who may benefit the immunotherapy. In addition, results from clinical trials explored combinatory therapeutic strategies with conventional and/or targeted therapy reported a higher efficacy with an acceptable safety profile in NSCLC treatments, as compared to the monotherapy of these agents alone. In this review article, we summarized several anti-PD-1/PD-L1 agents licensed for NSCLC treatment, with a focus on predictive biomarkers and companion diagnostic assays for identification of NSCLC patients for immunotherapy anti-PD-1/PDL1 antibodies. Of a great interest, potentials of the combinatory therapy of anti-PD-1/PDL1 therapy with a conventional or targeted therapy, or other immunotherapy such as CAR-T cell therapy were emphasized in the article.

show abstract

“…Furthermore, most NSCLC patients do not respond to immune checkpoint inhibitor monotherapy (8,9). Multiple combination modalities, including agents targeting EGFR, ALK, immune checkpoints and/or immunosuppressive tumor microenvironment, and chemotherapy are being tested; however, the longterm risks and benefits of these strategies in the treatment of NSCLC are currently unknown (10,11). A better understanding of the mechanisms regulating EGFR expression and activity will advance the biology of na€ ve tumors, and inform rational strategies for the personalized, multimodality management of aggressive NSCLC.…”

Section: Introductionmentioning

confidence: 99%

Dual Targeting of EGFR and IGF1R in the TNFAIP8 Knockdown Non–Small Cell Lung Cancer Cells

Day

Kallakury

Ross

et al. 2019

Molecular Cancer Research

View full text Add to dashboard Cite

Aberrant regulation of EGFR is common in non-small cell lung carcinomas (NSCLC), and tumor resistance to targeted therapies has been attributed to emergence of other cooccurring oncogenic events, parallel bypass receptor tyrosine kinase pathways including IGF1R, and TNFadriven adaptive response via NF-kB. TNFAIP8, TNFa-inducible protein 8, is an NF-kB-activated prosurvival and oncogenic molecule. TNFAIP8 expression protects NF-kB-null cells from TNFa-induced cell death by inhibiting caspase-8 activity. Here, we demonstrate that knockdown of TNFAIP8 inhibited EGF and IGF-1-stimulated migration in NSCLC cells. TNFAIP8 knockdown cells showed decreased level of EGFR and increased expression of sorting nexin 1 (SNX1), a key regulator of the EGFR trafficking through the endosomal compartments, and treatment with SNX1 siRNA partially restored EGFR expression in these cells. TNFAIP8 knockdown cells also exhibited downregulation of IGF-1-induced pIGF1R and pAKT, and increased expression of IGF-1-binding protein 3 (IGFBP3), a negative regulator of the IGF-1/IGF1R signaling. Consistently, treatment of TNFAIP8 knockdown cells with IGFBP3 siRNA restored pIGF1R and pAKT levels. TNFAIP8 knockdown cells had enhanced sensitivities to inhibitors of EGFR, PI3K, and AKT. Furthermore, IHC expression of TNFAIP8 was associated with poor prognosis in NSCLC. These findings demonstrate TNFAIP8-mediated regulation of EGFR and IGF1R via SNX1 and IGFBP3, respectively. We posit that TNFAIP8 is a viable, multipronged target downstream of the TNFa/NF-kB axis, and silencing TNFAIP8 may overcome adaptive response in NSCLC. Implications: TNFAIP8 and its effectors SNX1 and IGFBP3 may be exploited to improve the efficacy of molecular-targeted therapies in NSCLC and other cancers.

show abstract

Combination Immunotherapy in Non-small Cell Lung Cancer

Cited by 28 publications

References 59 publications

Tumor B7-H3 (CD276) Expression and Survival in Pancreatic Cancer

Tumor B7-H3 (CD276) Expression and Survival in Pancreatic Cancer

Anti-PD-1/PD-L1 Therapy for Non-Small-Cell Lung Cancer: Toward Personalized Medicine and Combination Strategies

Dual Targeting of EGFR and IGF1R in the TNFAIP8 Knockdown Non–Small Cell Lung Cancer Cells

Contact Info

Product

Resources

About