Correlating Immune Cell Infiltration Patterns with Recurrent Somatic Mutations in Advanced Clear Cell Renal Cell Carcinoma

Chakiryan, Nicholas H.; Hajiran, Ali; Kim, Young‐Chul; Aydın, Ahmet; Zemp, Logan; Katende, Esther N.; Fan, Wenyi; Cheng, Chia-Ho; Lopez-Blanco, Neale; Chahoud, Jad; Spiess, Philippe E.; Fournier, Michelle; Dhillon, Jasreman; Wang, Liang; Moran‐Segura, Carlos; Mulé, James J.; Du, Dongliang; Yoder, Sean; Berglund, Anders; Manley, Brandon

doi:10.1016/j.euf.2021.04.014

Cited by 14 publications

(13 citation statements)

References 29 publications

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“…Recently, lines of evidence have demonstrated that the immune infiltration participates in the progression of ccRCC. For instance, Chakiryan et al found that common somatic mutations in ccRCC may correlate with immune infiltration (33). Bai et al also found that various types of immune cells and the immune functions are correlated with ccRCC progression (34).…”

Section: Discussionmentioning

confidence: 99%

A New Prognostic Risk Signature of Eight Ferroptosis-Related Genes in the Clear Cell Renal Cell Carcinoma

et al. 2021

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Clear cell renal cell carcinoma (ccRCC) is the most common renal cell carcinoma and has poor prognosis in the locally advanced stage. Ferroptosis, a relatively new type of cell death, has gained significant attention in recent years. This study aimed to explore the prognostic value of ferroptosis-related genes (FRGs) in ccRCC. In this study, 50 differentially expressed FRGs between ccRCC and adjacent normal kidney tissues were identified, 26 of them correlated with overall survival (OS) (P <0.05). Eight optimal FRGs were selected by Lasso regression and multivariate Cox regression analysis, and used to construct a new prognostic risk signature to predict the prognosis of ccRCC patients. In addition, the signature passed the validation of prognostic survival analyses by a significant margin, and the risk score was identified as an independent prognostic marker via Cox regression analyses. Further studies indicated that the signature was significantly correlated with immune cell infiltration. Moreover, the levels of eight FRGs were examined in ccRCC. Collectively, the 8-FRG prognostic risk signature helps the clinicians predict the prognosis and OS of the patients, and standardize prognostic assessments.

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Section: Discussionmentioning

confidence: 99%

A New Prognostic Risk Signature of Eight Ferroptosis-Related Genes in the Clear Cell Renal Cell Carcinoma

et al. 2021

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“…Somatic mutational profiles often shape the tumor microenvironment immune type in most cancers ( Koh et al, 2019 ). Somatic mutation was highly correlated with immune cell infiltration and different immune infiltration patterns ( Chakiryan et al, 2021 ). Our results indicated LY96 expression was highly correlated with the somatic mutation profile in different types of cancers.…”

Section: Discussionmentioning

confidence: 99%

Pan-Cancer Analysis of the Characteristics of LY96 in Prognosis and Immunotherapy Across Human Cancer

Nie

Peng

et al. 2022

Front. Mol. Biosci.

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Lymphocyte antigen 96 (LY96) is implicated in tumorigenesis by modulating host immunity. However, an integrated pan-cancer analysis of LY96 in prognosis and immunotherapy across human cancers is still lacking. Therefore, we analyzed the LY96 expression and its prognostic role in tumors by multiple databases. We also investigated the correlation between LY96 and copy number, DNA methylation, somatic mutation, microsatellite instability (MSI), tumor mutation burden (TMB), tumor microenvironment (TME), and immune cell infiltration across human cancers. In addition, the biological processes related to LY96 across various tumors and the correlation between LY96 and 50% inhibitive concentration (IC50) of various drugs were investigated. We found that LY96 was differently expressed between tumor and normal tissues and was significantly upregulated in most types of cancers. LY96 was gradually upregulated from stages I to IV in several cancers. Moreover, we found LY96 may play a prognostic role in most cancers, and patients with high or low LY96 expression often show different clinical outcomes. LY96 was also associated with copy number, DNA methylation, somatic mutation, MSI, TMB, TME characteristics, and immune cell infiltration in cancers. LY96 may also regulate classic tumor-associated pathways in several cancers and is related to drug resistance. This article may help to elucidate the role of LY96 in tumorigenesis, which may promote the development of immunotherapy and targeted therapy in cancers.

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“…Interestingly, mutations affecting these chromatin-remodeling genes have also been associated with immunogenic features of several solid cancers. For instance, mutations in PBRM1 associate with increased CTL infiltration and PD-L1 expression, as well as with decreased infiltration by regulatory T cells in clear cell renal cell carcinoma [84,85]. In addition, mutations in PBRM1 were also found predictive for worse clinical outcomes after PD-L1 blockade in various cancers, including clear cell renal cell carcinoma and lung adenocarcinoma, highlighting the ambiguous role of PBRM1 in immunity [86].…”

Section: The Tumor Microenvironment In Sarcomas With Complex Genomesmentioning

confidence: 99%

Linking Immunity with Genomics in Sarcomas: Is Genomic Complexity an Immunogenic Trigger?

et al. 2021

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Sarcomas comprise a collection of highly heterogeneous malignancies that can be grossly grouped in the categories of sarcomas with simple or complex genomes. Since the outcome for most sarcoma patients has barely improved in the last decades, there is an urgent need for improved therapies. Immunotherapy, and especially T cell checkpoint blockade, has recently been a game-changer in cancer therapy as it produced significant and durable treatment responses in several cancer types. Currently, only a small fraction of sarcoma patients benefit from immunotherapy, supposedly due to a general lack of somatically mutated antigens (neoantigens) and spontaneous T cell immunity in most cancers. However, genomic events resulting from chromosomal instability are frequent in sarcomas with complex genomes and could drive immunity in those tumors. Improving our understanding of the mechanisms that shape the immune landscape of sarcomas will be crucial to overcoming the current challenges of sarcoma immunotherapy. This review focuses on what is currently known about the tumor microenvironment in sarcomas and how this relates to their genomic features. Moreover, we discuss novel therapeutic strategies that leverage the tumor microenvironment to increase the clinical efficacy of immunotherapy, and which could provide new avenues for the treatment of sarcomas.

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Correlating Immune Cell Infiltration Patterns with Recurrent Somatic Mutations in Advanced Clear Cell Renal Cell Carcinoma

Cited by 14 publications

References 29 publications

A New Prognostic Risk Signature of Eight Ferroptosis-Related Genes in the Clear Cell Renal Cell Carcinoma

A New Prognostic Risk Signature of Eight Ferroptosis-Related Genes in the Clear Cell Renal Cell Carcinoma

Pan-Cancer Analysis of the Characteristics of LY96 in Prognosis and Immunotherapy Across Human Cancer

Linking Immunity with Genomics in Sarcomas: Is Genomic Complexity an Immunogenic Trigger?

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