scholarly journals Influence of Sex in the Molecular Characteristics and Outcomes of Malignant Tumors

2021 ◽  
Vol 11 ◽  
Author(s):  
Jhajaira M. Araujo ◽  
Gina Rosas ◽  
Carolina Belmar-López ◽  
Luis E. Raez ◽  
Christian D. Rolfo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Immune Response ◽  
Immune System ◽  
Gene Set Enrichment Analysis ◽  
Molecular Characteristics ◽  
Cancer Type ◽  
Risk Of Death ◽  
Mutational Status ◽  
Immune System Development ◽  
Immune Pathways

BackgroundSex is frequently underestimated as a prognostic biomarker in cancer. In this study, we evaluated a large cohort of patients and public datasets to determine the influence of sex on clinical outcomes, mutational status, and activation of immune pathways in different types of cancer.MethodsA cohort of 13,619 Oncosalud-affiliated patients bearing sex-unrelated cancers was followed over a 20-year period. Hazard ratios (HRs) for death were estimated for female vs. male patients for each cancer type and then pooled in a meta-analysis to obtain an overall HR. In addition, the mutational status of the main actionable genes in melanoma (MEL), colorectal cancer (CRC), and lung cancer was compared between sexes. Finally, a gene set enrichment analysis (GSEA) of publicly available data was conducted, to assess differences in immune processes between sexes in MEL, gastric adenocarcinoma (GC), head and neck cancer (HNC), colon cancer (CC), liver cancer (LC), pancreatic cancer (PC), thyroid cancer (TC), and clear renal cell carcinoma (CCRCC).ResultsOverall, women had a decreased risk of death (HR = 0.73, CI95: 8%–42%), with improved overall survival (OS) in HNC, leukemia, lung cancer, lymphoma, MEL, multiple myeloma (MM), and non-melanoma skin cancer. Regarding the analysis of actionable mutations, only differences in EGFR alterations were observed (27.7% for men vs. 34.4% for women, p = 0.035). The number of differentially activated immune processes was higher in women with HNC, LC, CC, GC, MEL, PC, and TC and included cellular processes, responses to different stimuli, immune system development, immune response activation, multiorganism processes, and localization of immune cells. Only in CCRCC was a higher activation of immune pathways observed in men.ConclusionsThe study shows an improved survival rate, increased activation of immune system pathways, and an enrichment of EGFR alterations in female patients of our cohort. Enhancement of the immune response in female cancer patients is a phenomenon that should be further explored to improve the efficacy of immunotherapy.

scholarly journals 398 Towards new feeding approaches for optimizing nutritional status, immunity and host-microbiota interactions in neonatal and weaned piglets

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 181-181
Author(s):  
Martin Lessard ◽  
Mylène Blais ◽  
Guylaine Talbot ◽  
J Jacques Matte ◽  
Ann Letellier ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Intestinal Microbiota ◽  
System Development ◽  
Feed Additives ◽  
Epithelial Cell Line ◽  
Host Immune System ◽  
Gut Health ◽  
Weaned Piglets ◽  
Immune System Development

Abstract Lactation, feeding conditions, microbial interventions and piglet growth in the first few weeks of life have important impact on the intestinal microbiota establishment and immune system development of piglets. Indeed, colostrum and milk contain various bioactive components such as immune factors, antimicrobial peptides and oligosaccharides that contribute to maintain intestinal homeostasis and regulate interactions between microbiota and host immune system. Recent results revealed that low birth weight piglet (LBWP) with poor weight gain during the first two weeks of life develop different intestinal microbiota and immune response profiles compared to high BWP (HBWP) littermates. Consequently, piglets within litters may have different resilience to infections after weaning and benefit from feed additives in a specific manner. A study has been performed to evaluate the potential of bovine colostrum extract (BC) as replacement to plasma proteins for improving gut health and resilience to Salmonella infection in piglets. Results revealed that in weaned piglets fed BC, intestinal microbiota was differently modulated and bacterial dysbiosis induced by Salmonella was restored faster. Moreover, expression of genes involved in innate immunity such as β-defensin-2 and glutathione peroxidase-2 was respectively down- and up-regulated in BC fed piglets. A combination of dietary supplementation with BC, cupper and vitamins A and D has also been tested in LBWP and HBWP, and there is clear evidence that BC in combination with other feed additives promote growth and gut health in both LBWP and HBWP. The porcine intestinal epithelial cell line IPEC-J2 was used to better understand the functional properties of BC. Results indicated that BC improves wound healing, enhances barrier function and modulates the expression of several genes involved in innate immune response. Finally, as microbial intervention, the potential of fecal transplantation to modulate intestinal microbiota and immune system development of piglets is under investigation and will be discussed.

scholarly journals Respiratory Homeostasis and Exploitation of the Immune System for Lung Cancer Vaccines

2009 ◽  
Vol 05 (01) ◽  
pp. 40
Author(s):  
Adam Yagui-Beltrán ◽  
Lisa M Coussens ◽  
David M Jablons ◽  
◽  
◽  
...  
Keyword(s):  
Lung Cancer ◽  
Immune Response ◽  
Immune System ◽  
Cancer Vaccines ◽  
Molecular Mechanisms ◽  
Therapeutic Strategies ◽  
Lung Carcinogenesis ◽  
Respiratory Homeostasis ◽  
Novel Therapeutic Strategies ◽  
Novel Therapeutic

Lung cancer is the leading cause of all cancer deaths in the US. The international scientific and clinical community has made significant advances toward understanding specific molecular mechanisms underlying lung carcinogenesis; however, despite these insights and advances in surgery and chemoradiotherapy, the prognosis for non-small-cell lung cancer (NSCLC) remains poor. Nonetheless, significant effort is being focused on advancing translational research evaluating the efficacy of novel targeted therapeutic strategies for lung cancer. Illustrative examples of this include antagonists of the epidermal growth factor receptor (EGFR), tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib, and a diverse assortment of anti-angiogenic compounds targeting growth factors and/or their receptors that regulate tumorassociated angiogenic programs. In addition, with the increased awareness of the significant role chronically activated leukocytes play as potentiators of solid-tumor development, the role of innate and adaptive immune cells as regulators of lung carcinogenesis is being examined. While some of these studies are examining how novel therapeutic strategies may enhance the efficacy of lung cancer vaccines, others are evaluating the intrinsic characteristics of the immune response to lung cancer in order to identify rate-limiting molecular and/or cellular programs to target with novel anticancer therapeutics. In this article, we explore important aspects of the immune system and its role in regulating normal respiratory homeostasis compared with the immune response accompanying development of lung cancer. These hallmarks are then discussed in the context of recent efforts to develop lung cancer vaccines, where we have highlighted important concepts that must be taken into consideration for future development of novel therapeutic strategies and clinical trials assessing their efficacy.

scholarly journals Nivolumab Induces Impressive Complete Responses in Heavily Pretreated Classical Hodgkin Lymphoma (cHL): Immune System Reloaded in Case Series

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5369-5369
Author(s):  
Reyad Dada ◽  
Bassim T. Malas Al-Beirouti
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Conflicts Of Interest ◽  
Phase 1 ◽  
Performance Status ◽  
Single Agent ◽  
Case Series ◽  
System Response ◽  
Poor Performance Status ◽  
Cancer Type

Abstract Background: cHL is a histopathologically distinguish cancer type with an interesting microenvironment. The number of malignant cells is small in relation to the dominant T lymphocytes that have lost their antitumor activity through different mechanisms. Therefore, reactivation of host antitumoral immune response is promising approach to convert cHL in amenable disease for the immune system. Nivolumab is a novel antibody that binds to program death receptor-1 (PD-1) and prevents immune tolerance. Recently, several published clinical trials confirmed the clinical efficacy of single agent nivolumab in patients with few cancer types. Publications on nivolumab in cHL are very scarce. The available literature is limited to only one phase 1 (Ansell et al., N Engl J Med 2015;372:311-9) and another non-randomized phase 2 (Younes et al., Clin Oncol 34, 2016 (suppl; abstr 7535) clinical study that included 23 and 80 patients with relapsed/refractory cHL respectively. Case series: We report on three patients with heavily pretreatedcHL who failed several lines (mean 6.3, range: 3-9) of chemotherapy. Table 1 illustrates the patients' characteristics. All patients had stage IV disease at initiation of nivolumab. Two patients had very poor performance status (ECOG 3 and 4) attributed to progressivecHL and were oxygen dependent. One patient was wheelchair bound and the other was bedridden. The patients were started on single agent nivolumab 3 mg/kg every two weeks. Impressive clinical responses were observed in all patients after just one dose of nivolumab. In particular, significant rapid clinical improvement was obtained in both patients with the worst performance status. Both patients became mobile and self-dependent within 2-4 days after the first dose. This pattern of clinical response resembles that seen on the 1stday of immune response mediated recovery from viral respiratory infection. All patients reached complete metabolic response after 4 doses with continuous improvement of clinical condition. Both oxygen dependent patients became oxygen independent. No treatment related significant side effects were observed. Conclusion: Pre-treatedcHL is amenable to novel immunotherapy. Nivolumab induces impressive clinical and radiological responses with excellent tolerance. The drug enriches our treatments options by reloading the immune system response against cancer. Further clinical studies are needed to determine the effectiveness on large patients' cohort. Disclosures No relevant conflicts of interest to declare.

scholarly journals Do Transgenerational Epigenetic Inheritance and Immune System Development Share Common Epigenetic Processes?

2021 ◽  
Vol 9 (2) ◽  
pp. 20
Author(s):  
Rwik Sen ◽  
Christopher Barnes
Keyword(s):  
Immune Response ◽  
Immune System ◽  
System Development ◽  
Epigenetic Inheritance ◽  
Epigenetic Modifications ◽  
Future Research ◽  
Transgenerational Epigenetic Inheritance ◽  
Immune System Development ◽  
And Function

Epigenetic modifications regulate gene expression for development, immune response, disease, and other processes. A major role of epigenetics is to control the dynamics of chromatin structure, i.e., the condensed packaging of DNA around histone proteins in eukaryotic nuclei. Key epigenetic factors include enzymes for histone modifications and DNA methylation, non-coding RNAs, and prions. Epigenetic modifications are heritable but during embryonic development, most parental epigenetic marks are erased and reset. Interestingly, some epigenetic modifications, that may be resulting from immune response to stimuli, can escape remodeling and transmit to subsequent generations who are not exposed to those stimuli. This phenomenon is called transgenerational epigenetic inheritance if the epigenetic phenotype persists beyond the third generation in female germlines and second generation in male germlines. Although its primary function is likely immune response for survival, its role in the development and functioning of the immune system is not extensively explored, despite studies reporting transgenerational inheritance of stress-induced epigenetic modifications resulting in immune disorders. Hence, this review draws from studies on transgenerational epigenetic inheritance, immune system development and function, high-throughput epigenetics tools to study those phenomena, and relevant clinical trials, to focus on their significance and deeper understanding for future research, therapeutic developments, and various applications.

scholarly journals Embryonic hematopoiesis modulates the inflammatory response and larval hematopoiesis in Drosophila

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Wael Bazzi ◽  
Pierre B Cattenoz ◽  
Claude Delaporte ◽  
Vasanthi Dasari ◽  
Rosy Sakr ◽  
...  
Keyword(s):  
Immune Response ◽  
Transcription Factor ◽  
Immune System ◽  
System Development ◽  
Lineage Tracing ◽  
Developmental Pathway ◽  
Over Expression ◽  
Immune System Development ◽  
Immune Challenges ◽  
Stat Pathway

Recent lineage tracing analyses have significantly improved our understanding of immune system development and highlighted the importance of the different hematopoietic waves. The current challenge is to understand whether these waves interact and whether this affects the function of the immune system. Here we report a molecular pathway regulating the immune response and involving the communication between embryonic and larval hematopoietic waves in Drosophila. Down-regulating the transcription factor Gcm specific to embryonic hematopoiesis enhances the larval phenotypes induced by over-expressing the pro-inflammatory Jak/Stat pathway or by wasp infestation. Gcm works by modulating the transduction of the Upd cytokines to the site of larval hematopoiesis and hence the response to chronic (Jak/Stat over-expression) and acute (wasp infestation) immune challenges. Thus, homeostatic interactions control the function of the immune system in physiology and pathology. Our data also indicate that a transiently expressed developmental pathway has a long-lasting effect on the immune response.

scholarly journals Deciphering the Immune–Tumor Interplay During Early-Stage Lung Cancer Development via Single-Cell Technology

2022 ◽  
Vol 11 ◽  
Author(s):  
Wei-Wei Chen ◽  
Wei Liu ◽  
Yingze Li ◽  
Jun Wang ◽  
Yijiu Ren ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Immune Response ◽  
Immune System ◽  
Single Cell ◽  
Early Stage ◽  
Current Understanding ◽  
Cancer Development ◽  
Early Stage Lung Cancer ◽  
Cell Technology ◽  
Stage Lung Cancer

Lung cancer is the leading cause of cancer-related death worldwide. Cancer immunotherapy has shown great success in treating advanced-stage lung cancer but has yet been used to treat early-stage lung cancer, mostly due to lack of understanding of the tumor immune microenvironment in early-stage lung cancer. The immune system could both constrain and promote tumorigenesis in a process termed immune editing that can be divided into three phases, namely, elimination, equilibrium, and escape. Current understanding of the immune response toward tumor is mainly on the “escape” phase when the tumor is clinically detectable. The detailed mechanism by which tumor progenitor lesions was modulated by the immune system during early stage of lung cancer development remains elusive. The advent of single-cell sequencing technology enables tumor immunologists to address those fundamental questions. In this perspective, we will summarize our current understanding and big gaps about the immune response during early lung tumorigenesis. We will then present the state of the art of single-cell technology and then envision how single-cell technology could be used to address those questions. Advances in the understanding of the immune response and its dynamics during malignant transformation of pre-malignant lesion will shed light on how malignant cells interact with the immune system and evolve under immune selection. Such knowledge could then contribute to the development of precision and early intervention strategies toward lung malignancy.

scholarly journals Mosquito Innate Immunity

Insects ◽  
2018 ◽  
Vol 9 (3) ◽  
pp. 95 ◽  
Author(s):  
Ankit Kumar ◽  
Priyanshu Srivastava ◽  
PDNN Sirisena ◽  
Sunil Dubey ◽  
Ramesh Kumar ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immunity ◽  
Salivary Gland ◽  
Immune System ◽  
Innate Immune ◽  
Humoral Immune ◽  
Neural Tissues ◽  
Immune Pathways ◽  
Critical Overview ◽  
Mosquito Pathogen

Mosquitoes live under the endless threat of infections from different kinds of pathogens such as bacteria, parasites, and viruses. The mosquito defends itself by employing both physical and physiological barriers that resist the entry of the pathogen and the subsequent establishment of the pathogen within the mosquito. However, if the pathogen does gain entry into the insect, the insect mounts a vigorous innate cellular and humoral immune response against the pathogen, thereby limiting the pathogen’s propagation to nonpathogenic levels. This happens through three major mechanisms: phagocytosis, melanization, and lysis. During these processes, various signaling pathways that engage intense mosquito–pathogen interactions are activated. A critical overview of the mosquito immune system and latest information about the interaction between mosquitoes and pathogens are provided in this review. The conserved, innate immune pathways and specific anti-pathogenic strategies in mosquito midgut, hemolymph, salivary gland, and neural tissues for the control of pathogen propagation are discussed in detail.

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