Repeated observation of immune gene sets enrichment in women with non-small cell lung cancer

Araujo, Jhajaira M.; Prado, Alexandra; Cardenas, Nadezhda K.; Zaharia, Mayer; Dyer, Richard; Doimi, Franco D.; Bravo, Leny; Pinillos, Luis; Morante, Zaida; Aguilar, Alfredo; López, Luis Alberto Moreno; Gómez, Henry L.; Vallejos, Carlos S.; Rolfo, Christian; Pinto, Joseph A.

doi:10.18632/oncotarget.7943

Cited by 31 publications

(26 citation statements)

References 27 publications

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“…Conversely, women have a higher incidence of non-small cell lung cancer (NSCLC) [309], but have been shown to have better prognoses than males [29]. It has been suggested that sex differences in NSCLC are due to immune differences, as female NSCLC patients exhibit significantly different immune gene set enrichment compared to males [310].…”

Section: Sex Differences In the Immune Systemmentioning

confidence: 99%

Sex differences in cancer mechanisms

et al. 2020

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We now know that cancer is many different diseases, with great variation even within a single histological subtype. With the current emphasis on developing personalized approaches to cancer treatment, it is astonishing that we have not yet systematically incorporated the biology of sex differences into our paradigms for laboratory and clinical cancer research. While some sex differences in cancer arise through the actions of circulating sex hormones, other sex differences are independent of estrogen, testosterone, or progesterone levels. Instead, these differences are the result of sexual differentiation, a process that involves genetic and epigenetic mechanisms, in addition to acute sex hormone actions. Sexual differentiation begins with fertilization and continues beyond menopause. It affects virtually every body system, resulting in marked sex differences in such areas as growth, lifespan, metabolism, and immunity, all of which can impact on cancer progression, treatment response, and survival. These organismal level differences have correlates at the cellular level, and thus, males and females can fundamentally differ in their protections and vulnerabilities to cancer, from cellular transformation through all stages of progression, spread, and response to treatment. Our goal in this review is to cover some of the robust sex differences that exist in core cancer pathways and to make the case for inclusion of sex as a biological variable in all laboratory and clinical cancer research. We finish with a discussion of lab-and clinic-based experimental design that should be used when testing whether sex matters and the appropriate statistical models to apply in data analysis for rigorous evaluations of potential sex effects. It is our goal to facilitate the evaluation of sex differences in cancer in order to improve outcomes for all patients.

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Section: Sex Differences In the Immune Systemmentioning

confidence: 99%

Sex differences in cancer mechanisms

et al. 2020

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“…The specific CRs have previously been found to play specific roles in specific cancer types. For example, the lung adenocarcinoma (LUAD) specific DNA methylation eraser APOBEC3F has been found to play important roles in the immune response in non–small cell lung cancer ( 39 ). Another LUAD–specific DNA methylation eraser, APOBEC3C , has been reported to be significantly associated with a decreased risk of lung cancer ( 40 ).…”

Section: Resultsmentioning

confidence: 99%

FACER: comprehensive molecular and functional characterization of epigenetic chromatin regulators

et al. 2018

Nucleic Acids Research

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Epigenetic alterations, a well-recognized cancer hallmark, are driven by chromatin regulators (CRs). However, little is known about the extent of CR deregulation in cancer, and less is known about their common and specialized roles across various cancers. Here, we performed genome-wide analyses and constructed molecular signatures and network profiles of functional CRs in over 10 000 tumors across 33 cancer types. By integration of DNA mutation, genome-wide methylation, transcriptional/post-transcriptional regulation, and protein interaction networks with clinical outcomes, we identified CRs associated with cancer subtypes and clinical prognosis as potential oncogenic drivers. Comparative network analysis revealed principles of CR regulatory specificity and functionality. In addition, we identified common and specific CRs by assessing their prevalence across cancer types. Common CRs tend to be histone modifiers and chromatin remodelers with fundamental roles, whereas specialized CRs are involved in context-dependent functions. Finally, we have made a user-friendly web interface-FACER (Functional Atlas of Chromatin Epigenetic Regulators) available for exploring clinically relevant CRs for the development of CR biomarkers and therapeutic targets. Our integrative analysis reveals specific determinants of CRs across cancer types and presents a resource for investigating disease-associated CRs.

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“…Predictions linking tumor-infiltrating neutrophils and plasma cells to overall survival were validated by microscopy and IHC in lung adenocarcinoma [6]. Several groups have successfully applied CIBERSORT for cell deconvolution in various complex tissues, including microarray studies of peripheral blood [53], lung biopsies [54], triple negative breast cancers [55], and glioblastomas [56], and RNA-seq analyses of endometrial cancers [57]. …”

Section: Cell Deconvolution For Solid Tumorsmentioning

confidence: 99%

High-throughput genomic profiling of tumor-infiltrating leukocytes

Newman

Alizadeh

2016

Current Opinion in Immunology

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Tumors are complex ecosystems comprised of diverse cell types including malignant cells, mesenchymal cells, and tumor-infiltrating leukocytes (TILs). While TILs are well known to play important roles in many aspects of cancer biology, recent developments in immuno-oncology have spurred considerable interest in TILs, particularly in relation to their optimal engagement by emerging immunotherapies. Traditionally, the enumeration of TIL phenotypic diversity and composition in solid tumors has relied on resolving single cells by flow cytometry and immunohistochemical methods. However, advances in genome-wide technologies and computational methods are now allowing TILs to be profiled with increasingly high resolution and accuracy directly from RNA mixtures of bulk tumor samples. In this review, we highlight recent progress in the development of in silico tumor dissection methods, and illustrate examples of how these strategies can be applied to characterize TILs in human tumors to facilitate personalized cancer therapy.

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Repeated observation of immune gene sets enrichment in women with non-small cell lung cancer

Cited by 31 publications

References 27 publications

Sex differences in cancer mechanisms

Sex differences in cancer mechanisms

FACER: comprehensive molecular and functional characterization of epigenetic chromatin regulators

High-throughput genomic profiling of tumor-infiltrating leukocytes

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