P1.04-01 Impact of Chromatin Remodeling Genes Including SMARCA2 and PBRM1 on Neoantigen and Immune Landscape of NSCLC

Park, L.C.; Chang, Stephen; Ko, Tae-Kyung; Rhee, Kunsoo; Anker, Jonathan F.; Bhave, Mrinal; Davis, Alan T.; Cruz, M.T.; Iams, Wade T.; Zou, Lijuan; Wang, V.; Chuang, Jeffrey H.; Chae, Yoomi

doi:10.1016/j.jtho.2018.08.716

Cited by 2 publications

(5 citation statements)

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“…On the other hand, mutation or low expression of the chromatin remodelling genes, including SMARCA2 and PBRM1, is reported to be associated with larger neoantigen burdens and a greater amount of activated CD8 + T-cell infiltration in human non-small-cell lung carcinoma. 131,132 Tumours with low PBRM1 expression also show a favourable prognosis and are connected to the increase in cytotoxic lymphocytes in their TME. 133 Furthermore, ARID1A deficiency is correlated with a microsatellite instability genomic signature, a F I G U R E 5 Loss of PBAF could improve the expression of ISGs.…”

Section: Mutated Swi/snf Complexes Shape the Response Of Immunothermentioning

confidence: 99%

“…It has also been demonstrated that this subgroup of CRCs may possess a higher capacity to respond to monoclonal antibodies targeting PD‐1 and PD‐L1, further elucidating the relationship between the mutated SWI/SNF complexes and immunotherapy. On the other hand, mutation or low expression of the chromatin remodelling genes, including SMARCA2 and PBRM1 , is reported to be associated with larger neoantigen burdens and a greater amount of activated CD8 + T‐cell infiltration in human non–small‐cell lung carcinoma 131,132 . Tumours with low PBRM1 expression also show a favourable prognosis and are connected to the increase in cytotoxic lymphocytes in their TME 133 .…”

Section: Relationship Of the Swi/snf Complexes With Immunitymentioning

confidence: 99%

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The roles of mutated SWI/SNF complexes in the initiation and development of hepatocellular carcinoma and its regulatory effect on the immune system: A review

Lin

Yang

et al. 2020

Cell Proliferation

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Hepatocellular carcinoma (HCC) is a primary liver malignancy with a high global prevalence and a dismal prognosis. Studies are urgently needed to examine the molecular pathogenesis and biological characteristics of HCC. Chromatin remodelling, an integral component of the DNA damage response, protects against DNA damage‐induced genome instability and tumorigenesis by triggering the signalling events that activate the interconnected DNA repair pathways. The SWI/SNF complexes are one of the most extensively investigated adenosine triphosphate‐dependent chromatin remodelling complexes, and mutations in genes encoding SWI/SNF subunits are frequently observed in various human cancers, including HCC. The mutated SWI/SNF complex subunits exert dual functions by accelerating or inhibiting HCC initiation and progression. Furthermore, the abnormal SWI/SNF complexes influence the transcription of interferon‐stimulated genes, as well as the differentiation, activation and recruitment of several immune cell types. In addition, they exhibit synergistic effects with immune checkpoint inhibitors in the treatment of diverse tumour types. Therefore, understanding the mutations and deficiencies of the SMI/SNF complexes, together with the associated functional mechanisms, may provide a novel strategy to treat HCC through targeting the related genes or modulating the tumour microenvironment.

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Section: Mutated Swi/snf Complexes Shape the Response Of Immunothermentioning

confidence: 99%

Section: Relationship Of the Swi/snf Complexes With Immunitymentioning

confidence: 99%

The roles of mutated SWI/SNF complexes in the initiation and development of hepatocellular carcinoma and its regulatory effect on the immune system: A review

Lin

Yang

et al. 2020

Cell Proliferation

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“…Patients were selected from the cBioPortal for Cancer Genomics (http://cbioportal.org) which provides a digitalized resource for investigating cancer genomics data and their correlation with clinical outcome [3,4]. At the time of analysis, genetic data were available for 43,728 patients whereas survival and genetic data were available for 29,531 cancer patients of whom 1661 were treated with an ICI regimen [4]. Overall survival (OS) of ICI patients was defined as the time from the first infusion of treatment until death or last patient contact.…”

Section: To the Editormentioning

confidence: 99%

“…The presence of BAF/PBAF gene mutations was associated with improved outcome on immunotherapy in almost all carcinomas types except in non-small cell lung cancer (NSCLC), unknown primary carcinoma and renal cancer even if the effect for some cancer types did not reach statistical significance, due to limited sample size. Interestingly, a recent study has shown that mutation or low expression of BAF/PBAF genes including SMARCA2 and PBRM1 were associated with higher neoantigen burden and higher tumor infiltration of activated CD8 Tcells in NSCLC [4]. These data indicate that the impact of BAF/PBAF gene aberration on tumor Altogether, our findings establish a relationship between mutations in key genes encoding for components of the BAF/PBAF complex and outcome of patients treated with ICI and pave the way for clinical trials combining ICI with small-molecule inhibitors of chromatin remodeling pathways such as EZH2 inhibitors [5].…”

Section: To the Editormentioning

confidence: 99%

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Inactivating mutations in genes encoding for components of the BAF/PBAF complex and immune-checkpoint inhibitor outcome

et al. 2020

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Alterations of genes encoding subunits of the BAF/PBAF complexes are among the most frequent gene aberrations in human cancer. Such alterations have been shown to have an impact on tumor microenvironnement and on the capacity of tumors to respond to immune-checkpoint inhibitors (ICI). We analysed the clinical and genetic data from 43,728 patients accessed through cBioportal. The mutational frequencies of ARID1A, ARID1B, ARID2, PBRM1, SMARCA4, and SMARCB1 were 6.6%, 3,4, 3.4, 3.2, 4.1, and 1.2%, respectively. We then investigated the association between the presence of least one nonsynonymous somatic mutation of ARID1A, ARID1B, ARID2, PBRM1, SMARCA4, or SMARCB1 and overall survival of 1661 patients treated with an ICI. Across the entire cohort, patients with BAF/ PBAF mutated tumors have a statistically significant improvement in overall survival (median overall survival: 28 months [95% CI 21.6-34.3] versus 15 months [95% CI 12.9-17.0], p < 0.0001). When tumor mutational burden was adjusted for a multivariable Cox regression analysis, BAF/PBAF gene mutations remained an independent prognostic factor for overall survival in patients treated ICI. Our results establish a relationship between mutations in key genes encoding for components of the BAF/PBAF complex and outcome of patients treated with ICI. Further studies are needed to elucidate the underlying mechanisms of this interaction.

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P1.04-01 Impact of Chromatin Remodeling Genes Including SMARCA2 and PBRM1 on Neoantigen and Immune Landscape of NSCLC

Cited by 2 publications

References 0 publications

The roles of mutated SWI/SNF complexes in the initiation and development of hepatocellular carcinoma and its regulatory effect on the immune system: A review

The roles of mutated SWI/SNF complexes in the initiation and development of hepatocellular carcinoma and its regulatory effect on the immune system: A review

Inactivating mutations in genes encoding for components of the BAF/PBAF complex and immune-checkpoint inhibitor outcome

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