The effects of Fasciola hepatica recombinant proteins (peroxiredoxin and cathepsin L1) on Crohn's disease experimental model.

The immunomodulatory potential of the excretory-secretory (E/S) proteins of the helminths has been shown in previous investigations. This study evaluated the effects of the recombinants and excretory-secretory proteins of the Fasciola hepatica on induced colitis in Balb/c mice. The F. hepatica Recombinant proteins, Cathepsin L1 and Peroxiredoxin, and E/S proteins were intraperitoneally injected into the three mice groups as the case groups, while the control groups received PBS. Colitis was induced in mice by intraluminal administration of the 2, 4, 6-Trinitrobenzenesulfonic acid solution (TNBS). After 8 h, the case groups received the second dosage of the treatments, and it was repeated 24 h later. The immunological, pathological, and macroscopic changes were evaluated 3 days after colitis induction. The macroscopic evaluation revealed significantly lower inflammatory scores in the mice treated with recombinant Peroxiredoxin (rPRX) and recombinant Cathepsin L1 (rCL1). Despite the macroscopic observation, the pathological finding was insignificant between the groups. IFN-γ secretion was significantly lower in splenocytes of the groups that received rPRX, rCL1, and E/S than the controls. IL-10 showed significantly higher levels in groups treated with rPRX and rCL1 than controls, whereas the level of IL-4 was not statistically significant. Excretory-secretory proteins of the F. hepatica showed immunomodulatory potency and the main effects observed in this study were through the reduction of inflammatory cytokine and inflammation manifestation as well as induction of anti-inflammatory cytokines.

Natural killer cells in COVID-19: from infection, to vaccination and therapy.

Natural killer (NK) cells are among the most important innate immunity members, which are the first cells that fight against infected cells. The function of these cells is impaired in patients with COVID-19 and they are not able to prevent the spread of the disease or destroy the infected cells. Few studies have evaluated the effects of COVID-19 vaccines on NK cells, though it has been demonstrated that DNA vaccines and BNT162b2 can affect NK cell response. In the present paper, the effects of SARS-CoV-2 on the NK cells during infection, the effect of vaccination on NK cells, and the NK cell-based therapies were reviewed.

B cells and T cells abnormalities in patients with selective IgA deficiency.

BACKGROUND: Selective IgA deficiency (SIgAD) is the most prevalent inborn errors of immunity with almost unknown etiology. This study aimed to investigate the clinical diagnostic and prognostic values of lymphocyte subsets and function in symptomatic SIgAD patients. METHODS: A total of 30 available SIgAD patients from the Iranian registry and 30 age-sex-matched healthy controls were included in the present study. We analyzed B and T cell peripheral subsets and T cell proliferation assay by flow cytometry in SIgAD patients with mild and severe clinical phenotypes. RESULTS: Our results indicated a significant increase in naïve and transitional B cells and a strong decrease in marginal zone-like and switched memory B-cells in SIgAD patients. We found that naïve and central memory CD4+ T cell subsets, as well as Th1, Th2 and regulatory T cells, have significantly decreased. On the other hand, there was a significant reduction in central and effector memory CD8+ T cell subsets, whereas proportions of both (CD4+ and CD8+) terminally differentiated effector memory T cells (TEMRA) were significantly elevated in our patients. Although some T cell subsets in severe SIgAD were similar, a decrease in marginal-zone and switched memory B cells and an increase in CD21low B cell of severe SIgAD patients were slightly prominent. Moreover, the proliferation activity of CD4+ T cells was strongly impaired in SIgAD patients with a severe phenotype. CONCLUSION: SIgAD patients have varied cellular and humoral deficiencies. Therefore, T cell and B cell assessment might help in better understanding the heterogeneous pathogenesis and prognosis estimation of the disease.

Clinical and Immunologic Characteristics of Non-Hematologic Cancers in Patients with Inborn Errors of Immunity.

Inborn errors of immunity (IEI) are a heterogeneous group of inherited disorders, and almost 500 genes associated with these disorders have been identified. Defects in IEI genes lead to diverse clinical manifestations including increased susceptibility to recurrent or prolonged infections, immune dysregulation phenotypes (such as severe atopy, allergy, autoimmunity, and uncontrolled inflammation, lymphoproliferation), as well as predisposition to malignancies. Although the majority of IEI patients present hematologic cancers, the characteristics of other types of cancers are not well described in these groups of patients. By investigating 5384 IEI patients registered in the Iranian national registry the clinical and immunologic phenotypes of patients with non-hematologic cancers were compared with other malignant and non-malignant patients. Solid tumors were reported <20% of malignant IEI patients (n = 27/144 patients) and appeared to be very heterogeneous by type and localization as well as molecular defects (mainly due to DNA repair defect resulted from ATM deficiency). The correlation between the type of malignancy and survival status was remarkable as patients with non-hematologic cancers survive higher than IEI patients with hematologic cancers. Our findings showed that different types of malignancy could be associated with specific entities of IEI. Therefore, the education of physicians about the risk of malignancies in IEI is required for personalized treatment and appropriate management of patients.

Diversity of malignancies in patients with different types of inborn errors of immunity.

Genetic defects in the development, maturation, and/or function of the immune cells can lead to Inborn errors of immunity (IEI) which may predispose patients to malignancies. The overall risk for cancer in children with IEI ranges from 4 to 25% and the type of malignancy is highly dependent on the specific mutant gene underlying IEI. We investigated 3056 IEI patients registered in the Iranian national registry between the years 1999 and 2020 in this retrospective cohort study. The frequency of malignancy and its association with the type of IEI in these patients were evaluated. A total of 82 IEI patients with malignancy were enrolled in this study. Among them, predominantly lymphoma was the most common type of malignancy (67.1%), followed by leukemia (11%), and cancers of the head and neck (7.3%). Among identified lymphoma cancers, non-Hodgkin's lymphomas were the most frequent type (43.9%) followed by different subtypes of Hodgkin's lymphoma (23.2%). Solid tumors (18.3%) appeared to be very heterogeneous by type and localization. The correlation between the type of malignancy and survival status and the association between the type of malignancy and IEI entities were unremarkable. The awareness of the association between the presence of IEI and cancer highlights the importance of a synergistic effort by oncologists and immunologists in the early diagnosis of malignancy and personalized therapeutic strategies in IEI patients.

Role of NKT cells in cancer immunotherapy-from bench to bed.

Natural killer T (NKT) cells are a specific T cell subset known to express the αß-T cell receptor (TCR) for antigens identification and express typical NK cell specifications, such as surface expression of CD56 and CD16 markers as well as production of granzyme. Human NKT cells are divided into two subgroups based on their cytokine receptor and TCR repertoire. Both of them are CD1-restricted and recognize lipid antigens presented by CD1d molecules. Studies have demonstrated that these cells are essential in defense against malignancies. These cells secret proinflammatory and regulatory cytokines that stimulate or suppress immune system responses. In several murine tumor models, activation of type I NKT cells induces tumor rejection and inhibits metastasis's spread. However, type II NKT cells are associated with an inhibitory and regulatory function during tumor immune responses. Variant NKT cells may suppress tumor immunity via different mechanisms that require cross-talk with other immune-regulatory cells. NKT-like cells display high tumor-killing abilities against many tumor cells. In the recent decade, different studies have been performed based on the application of NKT-based immunotherapy for cancer therapy. Moreover, manipulation of NKT cells through administering autologous dendritic cell (DC) loaded with α-galactosylceramide (α-GalCer) and direct α-GalCer injection has also been tested. In this review, we described different subtypes of NKT cells, their function in the anti-tumor immune responses, and the application of NKT cells in cancer immunotherapy from bench to bed.

Tumor-promoting myeloid cells in the pathogenesis of human oncoviruses: potential targets for immunotherapy.

Oncoviruses, known as cancer-causing viruses, are typically involved in cancer progression by inhibiting tumor suppressor pathways and uncontrolled cell division. Myeloid cells are the most frequent populations recruited to the tumor microenvironment (TME) and play a critical role in cancer development and metastasis of malignant tumors. Tumor-infiltrating myeloid cells, including tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), tumor-associated dendritic cells (TADCs), and tumor-associated neutrophils (TANs) exert different states from anti-tumorigenic to pro-tumorigenic phenotypes in TME. Although their role in the anti-tumorigenic state is well introduced, their opposing roles, pro-tumorigenic activities, such as anti-inflammatory cytokine and reactive oxygen species (ROS) production, should not be ignored since they result in inflammation, tumor progression, angiogenesis, and evasion. Since the blockade of these cells had promising results against cancer progression, their inhibition might be helpful in various cancer immunotherapies. This review highlights the promoting role of tumor-associated myeloid cells (TAMCs) in the pathophysiology of human virus tumorigenesis.

Plumbagin attenuates Bleomycin-induced lung fibrosis in mice.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a fatal fibrotic lung disease with limited treatment options. Plumbagin (PL) is an herbal extract with diverse pharmacological effects that have been recently used to treat various types of cancer. This study aims to explore the anti-fibrotic effect of PL and possible underlying mechanisms in IPF. METHODS: We used a bleomycin-induced experimental mouse model of lung fibrosis to assess the potential anti-fibrotic effect of PL. Histological analysis of lung tissue samples by H&E and Masson's trichrome staining and hydroxyproline assay was performed to evaluate the fibrotic alterations. ELISA and real-time quantitative PCR were conducted to determine the amount of tumor necrosis factor-alpha (TNFα), tumor growth factor-beta (TGF-ß), connective tissue growth factor (CTGF), and endothelin-1 (ET-1). RESULTS: Bleomycin exposure induced lung fibrosis, which was indicated by inflammation, collagen deposition, and structural damage. PL remarkably prevented bleomycin-induced lung fibrosis. Furthermore, PL significantly inhibited TNF-α and TGF-ß production. PL also diminished the upregulated expression of CTGF and ET-1 induced by bleomycin. CONCLUSION: Overall, our findings suggest PL as an anti-fibrotic agent acting via down-regulation of TGF-ß/CTGF or ET-1 axis, as well as TNF-α, to improve lung fibrosis.

Functional prominence of natural killer cells and natural killer T cells in pregnancy and infertility: A comprehensive review and update.

During pregnancy, complicated connections are formed between a mother and a fetus. In a successful pregnancy, the maternal-fetal interface is affected by dynamic changes, and the fetus is protected against the mother's immune system. Natural killer (NK) cells are one of the immune system cells in the female reproductive system that play an essential role in the physiology of pregnancy. NK cells not only exist in peripheral blood (PB) but also can exist in the decidua. Studies have suggested multiple roles for these cells, including decidualization, control of trophoblast growth and invasion, embryo acceptance and maintenance by the mother, and facilitation of placental development during pregnancy. Natural killer T (NKT) cells are another group of NK cells that play a crucial role in the maintenance of pregnancy and regulation of the immune system during pregnancy. Studies show that NK and NKT cells are not only effective in maintaining pregnancy but also can be involved in infertility-related diseases. This review focuses on NK and NKT cells biology and provides a detailed description of the functions of these cells in implantation, placentation, and immune tolerance during pregnancy and their role in pregnancy complications.

Prevalence of Hepatitis in Prisoners: A Systematic Review of Current Evidence.

INTRODUCTION: Prisoners represent high-risk behaviors such as injecting drug use, sharing syringes, tattooing, and unprotected sexual intercourse. The authors aimed to study the prevalence of hepatitis B, hepatitis C, and hepatitis D in the prisoners. METHODS: We conducted a systematic search using the keywords in online databases of PubMed, Web of Science, Scopus, and Science Direct. Two independent researchers examined the quality of the articles and the probable risk of bias. The most relevant articles by title and abstract were retrieved. Finally, the full text of selected articles was read, and the critical findings were extracted. RESULTS: Reviews of 23 studies showed that most prisoners are susceptible to hepatitis B and hepatitis C. One study also indicated that prisoners could be infected with hepatitis A and hepatitis E. The most common routes of hepatitis transmission in prisons were intravenous drug use, needle sharing, tattooing, and unsafe sex with multiple sexual partners. CONCLUSION: High-risk sexual behaviors, shared contaminated needles for IV drug injection, and tattooing are the principal routes of hepatitis transmission among prison inmates. Hepatitis treatment is feasible and could be useful for infected prisoners undergoing a well-designed treatment program.

Circulating CTRP5 in rheumatoid arthritis: an exploratory biomarker study.

BACKGROUND: Rheumatoid arthritis (RA) is an inflammatory disease that is characterized by the overproduction of cytokines. Among the newly discovered cytokines are the adipokines which are primarily produced by and released from the adipose tissue and some immune cells, as well as synovial cells. they are involved in various immune responses and inflammatory processes. However, there are controversial data regarding the pro-inflammatory or anti-inflammatory effects of adipokines in different conditions. C1q/TNF-related protein 5 (CTRP5) is a newly identified adipokine and adiponectin paralogous protein, which has been shown to be correlated with inflammatory diseases. Accordingly, the present study was designed to investigate the serum levels of CTRP5 in RA patients and evaluate any possible alterations in comparison to healthy individuals. METHODS: Serum CTRP-5 levels were measured in 46 patients and 22 healthy controls by ELISA. The demographic, laboratory, and clinical features of the patients were also evaluated in order to find any correlations. RESULTS: Serum levels of CTRP-5 were significantly (p < 0.0001) higher in patients with RA (14.88 ± 25.55) compared to healthy controls (4.262 ± 2.374). There was a significant correlation between serum CTRP-5 levels and triglyceride (TG) (r: - 0.3010, p: 0.0498), as well as erythrocyte sedimentation rate (ESR) (r: 0.3139, p: 0.0457), C-reactive protein (CRP) (r: 0.5140, p: 0.0008), and the number of white blood cells (WBC) (r: 0.3380, p: 0.0307), which are considered as the markers indicating the extent of inflammation. Moreover, CTRP-5 was found to be correlated with interstitial lung disease (ILD) (r: 0.3416, p: 0.0385), a comorbidity associated with RA disease. CONCLUSION: This study demonstrated the increased level of circulating CTRP-5 in RA patients, which correlated with some inflammation-associated parameters and RA-associated comorbidities. Our observations suggest CTRP-5 as a putative inflammatory biomarker in RA, which may be useful besides the other disease-related markers.

The mutations frequency of enhancer II/HBx regions of hepatitis B virus in acutely infected Iranian patients: a cross-sectional study.

Background and Objectives: The viral transactivator HBx protein affect cellular, viral and pregenomic factors pathway. Mutations in this protein can produce new viruses with new antigenic determinants that are generally related to developing cancerous. Materials and Methods: In this cross-sectional study, 33 serum samples of patients diagnosed with acute HBV infection were investigated for HBeAg and HBV DNA viral load and HBx gene mutations. mutation in the HBx protein detected by sequencing analysis. Results: Out of the 33 samples, 19 samples were males (57.6%), and 14 samples were females. 15 (45.5%) were positive for HBx DNA and 18 patients were negative for HBx DNA (54.5%). After sequencing, three mutations were recognized in HBx at nucleotide positions 147, 148, and 391 that were stationed to G1524A, G1525A, and G1767C mutations. Conclusion: The analysis result of this study shows G1524A and G1525A mutations that an important role in altering the inhibition function of the HBx activity domain. The G1767C mutation inactivates HBx transactivation activity. These mutations have a critical role in the pathogenicity of the virus, and the intensity of hepatic tissue demolition and the development of cirrhosis or carcinoma in patients can be understood.

Construction of circRNA-miRNA-mRNA network in the pathogenesis of recurrent implantation failure using integrated bioinformatics study.

This research attempted to elucidate the molecular components are involved in the pathogenesis of recurrent implantation failure (RIF). We initially identified that 386 mRNAs, 144 miRNAs and 2548 circRNAs were differentially expressed (DE) in RIF and then investigated the genetic cause of the observed abnormal expression by constructing a circRNA-miRNA-mRNA network considering the competing endogenous RNA theory. We further analysed the upstream transcription factors and related kinases of DEmRNAs (DEMs) and demonstrated that SUZ12, AR, TP63, NANOG, and TCF3 were the top five TFs binding to these DEMs. Besides, protein-protein interaction analysis disclosed that ACTB, CXCL10, PTGS2, CXCL12, GNG4, AGT, CXCL11, SST, PENK, and FOXM1 were the top 10 hub genes in the acquired network. Finally, we performed the functional enrichment analysis and found that arrhythmogenic right ventricular cardiomyopathy (ARVC), hypertrophic cardiomyopathy (HCM), pathways in cancer, TNF signalling pathway and steroid hormone biosynthesis were the potentially disrupted pathways in RIF patients. Optimistically, our findings may deepen our apprehensions about the underlying molecular and biological causes of RIF and provide vital clues for future laboratory and clinical experiments that will ultimately bring a better outcome for patients with RIF.

Progesterone Aggravates Lung Fibrosis in a Mouse Model of Systemic Sclerosis.

Background: Gender-related factors have explained the higher prevalence of autoimmune diseases in women. Sex hormones play a key role in the immune system and parenchymal cells function; therefore, these hormones can be important in the pathogenesis of autoimmune diseases as a risk or beneficial factor. Lung fibrosis is the main cause of mortality in systemic sclerosis, a female predominant autoimmune disease. The objective of this study was to examine the effect of progesterone on lung fibrosis in a mouse model of systemic sclerosis. Methods: Mice with bleomycin-induced lung fibrosis treated with progesterone subcutaneously for 21 and 28 days. Blood was collected for hormone and cytokine measurement at the end of treatment then, skin and lung tissues were harvested for histological assessment, gene expression, cytokine, hydroxyproline, and gelatinase measurement. Results: Trichrome staining and hydroxyproline measurements showed that progesterone treatment increased the content of collagen in fibrotic and normal lung tissues. Progesterone increased α-SMA (P < 0.01), TGF- ß (P < 0.05) and decreased MMP9 (P < 0.05) in fibrotic lung tissues. Also progesterone treatment decreased the gene expression of Col1a2 (P <0.05), Ctgf (P <01), End1 (0.001) in bleomycin- injured lung tissues. The serum level of TNF-α was decreased, but the serum level of cortisol was increased by progesterone treatment in fibrotic mice (P< 0.05). Conclusion: Our results showed that progesterone aggravates lung fibrosis in a mouse model of systemic sclerosis.

Host factors: Implications in immunopathogenesis of COVID-19.

Coronavirus disease 2019 (COVID-19) is a viral disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 is more serious in people with underlying diseases, but the cause of healthy people with progressive disease is largely unknown. Host genetic factors such as ACE2 variants, IFITM-3, HLA, TMRSS2, and furin polymorphisms appear to be one of the agents involved in the progression of the COVID-19 and outcome of the disease. This review discusses the general characteristics of SARS-CoV-2, including viral features, receptors, cell entry, clinical findings, and the main human genetic factors that may contribute to the pathogenesis of COVID-19 and get the patients' situation more complex. Further knowledge in this context may help to find a way to prevent and treat this viral pneumonia.

Overexpression of HPRT1 is associated with poor prognosis in head and neck squamous cell carcinoma.

Hypoxanthine phosphoribosyltransferase (HPRT1), as a salvage pathway enzyme, plays a crucial role in modulating the cell cycle and has been reported to be overexpressed in multiple cancers. Nevertheless, the relationship between the HPRT1 gene and head and neck squamous cell carcinomas (HNSCCs) has not been investigated so far. In this study, we first evaluated the expression and clinical value of HPRT1 mRNA and protein in tumor and healthy control tissues. Then, we examined mutations of the HPRT1 gene and their association with survival outcomes of patients with HNSCC. We also performed functional analyses of HPRT1 coexpressed genes and examined the association between HPRT1 expression and drug sensitivity. Both HPRT1 mRNA and protein were significantly higher in HNSCC compared with normal tissues, and up-regulation of HPRT1 was also correlated with age, sex, pathological stage and histological grades of patients with HNSCC. Moreover, HPRT1 and its associated genes were observed to be enriched for several cancer-related pathways, including DNA replication and cell cycle. Finally, patients exhibiting overexpression of the HPRT1 gene may be resistant to abiraterone and sensitive to several drugs, including tozasertib and teniposide. This study demonstrated that the elevated expression of HPRT1 gene is correlated with the progression of HNSCC; thus, this gene may serve as a useful indicator for the early detection, risk stratification and targeted therapy of patients with HNSCC.

Implications the Role of miR-155 in the Pathogenesis of Autoimmune Diseases.

MicroRNAs (miRNAs) are small noncoding conserved RNAs containing 19 to 24 nucleotides that are regulators of post-translational modifications and are involved in the majority of biological processes such as immune homeostasis, T helper cell differentiation, central and peripheral tolerance, and immune cell development. Autoimmune diseases are characterized by immune system dysregulation, which ultimately leads to destructive responses to self-antigens. A large body of literature suggests that autoimmune diseases and immune dysregulation are associated with different miRNA expression changes in the target cells and tissues of adaptive or innate immunity. miR-155 is identified as a critical modulator of immune responses. Recently conducted studies on the expression profile of miR-155 suggest that the altered expression and function of miR-155 can mediate vulnerability to autoimmune diseases and cause significant dysfunction of the immune system.

Immune checkpoints and cancer development: Therapeutic implications and future directions.

Over the past few decades, different inhibitory receptors have been identified, which have played prominent roles in reducing anti-tumor immune responses. The role of immune checkpoint inhibitors in cancer was revealed by critical blockade of the cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and programmed cell death protein-1 (PD-1) checkpoints. Immune checkpoint inhibitors, including anti-PD-1 (nivolumab and pembrolizumab), anti-PD-L1 (Atezolizumab, avelumab, and duravulumab), and anti-CTLA-4 (ipilimumab, tremelimumab), are currently FDA-approved treatment options for a broad range of cancer types. However, regarding immunotherapy advances in recent years, most studies have been focused on finding the antibodies against other inhibitory immune checkpoints in the tumor microenvironment such as lymphocyte activation gene-3 (LAG-3), T cell immunoglobulin, and mucin domain 3 (TIM-3), B7-homolog 3 (B7-H3), V-domain immunoglobulin-containing suppressor of T-cell activation (VISTA), diacylglycerol kinase-α (DGK-α), T cell immunoglobulin and ITIM domain (TIGIT), and B and T lymphocyte attenuator (BTLA). This immune checkpoint exerts differential inhibitory impacts on various types of lymphocytes. The suppression of immune responses demonstrates a surprising synergy with PD-1. Therefore, most antibodies against these immune checkpoints are undertaking clinical trials for cancer immunotherapy of advanced solid tumors and hematologic malignancies. In this review, we will summarize recent findings of immune checkpoint and the role of monoclonal antibodies in cancer immunotherapy targeting these receptors.

Autoimmune manifestations among 461 patients with monogenic inborn errors of immunity.

BACKGROUND: The inborn errors of immunity (IEIs) are a group of heterogeneous disorders mainly characterized by severe and recurrent infections besides other complications including autoimmune and inflammatory diseases. In this study, we aim to evaluate clinical, immunologic, and molecular data of monogenic IEI patients with and without autoimmune manifestations. METHODS: We have retrospectively screened cases of monogenic IEI in the Iranian PID registry for the occurrence of autoimmunity and immune dysregulation. A questionnaire was filled for all qualified patients with monogenic defects to evaluate demographic, laboratory, clinical, and molecular data. RESULTS: A total of 461 monogenic IEI patients (290 male and 171 female) with a median (IQR) age of 11.0 (6.0-20.0) years were enrolled in this study. Overall, 331 patients (72.1%) were born to consanguineous parents. At the time of the study, 330 individuals (75.7%) were alive and 106 (24.3%) were deceased. Autoimmunity was reported in 92 (20.0%) patients with a median (IQR) age at autoimmune diagnosis of 4.0 (2.0-7.0) years. Sixteen patients (3.5%) showed autoimmune complications (mostly autoimmune cytopenia) as the first presentation of the disease. Most of the patients with autoimmunity were diagnosed clinically with common variable immunodeficiency (42.4%). The frequency of sinusitis and splenomegaly was significantly higher in patients with autoimmunity than patients without autoimmunity. In patients with autoimmunity, the most common pathogenic variants were identified in LRBA (in 21 patients, 23.0%), ATM (in 13 patients, 14.0%), and BTK (in 9 patients, 10.0%) genes. In the evaluation of autoimmunity by different genes, 4 of 4 IL10RB (100%), 3 of 3 AIRE (100%), and 21 of 30 LRBA (70.0%) mutated genes had the highest prevalence of autoimmunity. CONCLUSIONS: Autoimmune phenomena are common features among patients with monogenic IEI and are associated with a more complicated course of the disease. Therefore, when encountering autoimmune disorders, especially in the setting of dysgammaglobulinemia, it would be appropriate to conduct next-generation sequencing to discover responsible genes for the immune dysregulation at an early stage of the disease.

ACE2 correlates with immune infiltrates in colon adenocarcinoma: Implication for COVID-19.

Novel coronavirus disease (COVID-19) pandemic has become a global health emergency. It has been reported that a few conditions, including cancer, predispose individuals to SARS-CoV-2 infection and severe form of COVID-19. These findings led us to evaluate the susceptibility of colon adenocarcinoma (COAD) patients to SARS-CoV-2 infection by investigating ACE2 expression in their tumor tissues. The expression analysis revealed that both mRNA and protein levels of ACE2 had increased in colon cancer samples than normal group. Next, the prognosis analysis has indicated that the upregulation of ACE2 was not correlated with patient survival outcomes. Further assessment displayed the hypomethylation of the ACE2 gene promoter in COAD patients. This methylation status has a strong negative correlation with ACE2 gene expression. The functional enrichment analysis of the genes that had similar expression patterns with ACE2 in colon cancer tissues demonstrated that they mainly enriched in Vitamin digestion and absorption pathway. Finally, we found that ACE2 gene expression had a significant association with the immune cell infiltration levels in COAD patients. In conclusion, it has plausible that COAD patients are more likely to be infected with SARS-CoV-2 and experience severe injuries. Moreover, COVID-19 would bring unfavorable survival outcomes for patients with colon cancer by way of immune cell infiltration linked process. The present study highlights the importance of preventiveactionsfor COAD patients during the COVID-19 pandemic.