Gnotobiotic Mouse Immune Response Induced by Bifidobacterium sp. Strains Isolated from Infants

ABSTRACT Bifidobacterium, which is a dominant genus in infants’ fecal flora and can be used as a probiotic, has shown beneficial effects in various pathologies, including allergic diseases, but its role in immunity has so far been little known. Numerous studies have shown the crucial role of the initial intestinal colonization in the development of the intestinal immune system, and bifidobacteria could play a major role in this process. For a better understanding of the effect of Bifidobacterium on the immune system, we aimed at determining the impact of Bifidobacterium on the T-helper 1 (TH1)/TH2 balance by using gnotobiotic mice. Germfree mice were inoculated with Bifidobacterium longum NCC2705, whose genome is sequenced, and with nine Bifidobacterium strains isolated from infants’ fecal flora. Five days after inoculation, mice were killed. Transforming growth factor β1 (TGF-β1), interleukin-4 (IL-4), IL-10, and gamma interferon (IFN-γ) gene expressions in the ileum and IFN-γ, tumor necrosis factor alpha (TNF-α), IL-10, IL-4, and IL-5 secretions by splenocytes cultivated for 48 h with concanavalin A were quantified. Two Bifidobacterium species had no effect (B. adolescentis) or little effect (B. breve) on the immune system. Bifidobacterium bifidum, Bifidobacterium dentium, and one B. longum strain induced TH1 and TH2 cytokines at the systemic and intestinal levels. One B. longum strain induced a TH2 orientation with high levels of IL-4 and IL-10, both secreted by splenocytes, and of TGF-β gene expression in the ileum. The other two strains induced TH1 orientations with high levels of IFN-γ and TNF-α splenocyte secretions. Bifidobacterium's capacity to stimulate immunity is species specific, but its influence on the orientation of the immune system is strain specific.

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Coexistent Malnutrition Is Associated with Perturbations in Systemic and Antigen-Specific Cytokine Responses in Latent Tuberculosis Infection

Clinical and Vaccine Immunology ◽

10.1128/cvi.00009-16 ◽

2016 ◽

Vol 23 (4) ◽

pp. 339-345 ◽

Cited By ~ 17

Author(s):

Rajamanickam Anuradha ◽

Saravanan Munisankar ◽

Yukthi Bhootra ◽

Nathalla Pavan Kumar ◽

Chandrakumar Dolla ◽

...

Keyword(s):

Transforming Growth Factor Beta ◽

Transforming Growth Factor ◽

Interleukin 4 ◽

Cytokine Responses ◽

Increased Risk ◽

Tnf Α ◽

Latent Tb ◽

Low Bmi ◽

Ifn Γ

ABSTRACTMalnutrition, as defined by low body mass index (BMI), is a major risk factor for the development of active tuberculosis (TB), although the biological basis underlying this susceptibility remains poorly characterized. To verify whether malnutrition affects the systemic and antigen-specific cytokine levels in individuals with latent TB (LTB), we examined circulating and TB antigen-stimulated levels of cytokines in individuals with LTB and low BMI (LBMI) and compared them with those in individuals with LTB and normal BMI (NBMI). Coexistent LBMI with LTB was characterized by diminished circulating levels of type 1 (gamma interferon [IFN-γ] and tumor necrosis factor alpha [TNF-α]), type 2 (interleukin-4 [IL-4]), type 17 (IL-22), and other proinflammatory (IL-1α, IL-1β, and IL-6) cytokines but elevated levels of other type 2 (IL-5 and IL-13) and regulatory (IL-10 and transforming growth factor beta [TGF-β]) cytokines. In addition, LBMI with LTB was associated with diminished TB antigen-induced IFN-γ, TNF-α, IL-6, IL-1α, and IL-1β levels. Finally, there was a significant positive correlation between BMI values and TNF-α and IL-1β levels and a significant negative correlation between BMI values and IL-2, IL-10, and TGF-β levels in individuals with LTB. Therefore, our data reveal that latent TB with a coexistent low BMI is characterized by diminished protective cytokine responses and heightened regulatory cytokine responses, providing a potential biological mechanism for the increased risk of developing active TB.

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Decitabine Promotes Modulation in Phenotype and Function of Monocytes and Macrophages That Drive Immune Response Regulation

Cells ◽

10.3390/cells10040868 ◽

2021 ◽

Vol 10 (4) ◽

pp. 868

Author(s):

Fabiana Albani Zambuzi ◽

Priscilla Mariane Cardoso-Silva ◽

Ricardo Cardoso Castro ◽

Caroline Fontanari ◽

Flavio da Silva Emery ◽

...

Keyword(s):

Immune Response ◽

Hematological Malignancies ◽

M2 Macrophage ◽

M2 Polarization ◽

Tnf Α ◽

Monocytes And Macrophages ◽

Ifn Γ ◽

And Function ◽

The Impact

Decitabine is an approved hypomethylating agent used for treating hematological malignancies. Although decitabine targets altered cells, epidrugs can trigger immunomodulatory effects, reinforcing the hypothesis of immunoregulation in treated patients. We therefore aimed to evaluate the impact of decitabine treatment on the phenotype and functions of monocytes and macrophages, which are pivotal cells of the innate immunity system. In vitro decitabine administration increased bacterial phagocytosis and IL-8 release, but impaired microbicidal activity of monocytes. In addition, during monocyte-to-macrophage differentiation, treatment promoted the M2-like profile, with increased expression of CD206 and ALOX15. Macrophages also demonstrated reduced infection control when exposed to Mycobacterium tuberculosis in vitro. However, cytokine production remained unchanged, indicating an atypical M2 macrophage. Furthermore, when macrophages were cocultured with lymphocytes, decitabine induced a reduction in the release of inflammatory cytokines such as IL-1β, TNF-α, and IFN-γ, maintaining IL-10 production, suggesting that decitabine could potentialize M2 polarization and might be considered as a therapeutic against the exacerbated immune response.

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Intestinal Intraepithelial Lymphocytes Sustain the Epithelial Barrier Function against Eimeria vermiformis Infection

Infection and Immunity ◽

10.1128/iai.02024-05 ◽

2006 ◽

Vol 74 (9) ◽

pp. 5292-5301 ◽

Cited By ~ 68

Author(s):

Kyoko Inagaki-Ohara ◽

Fitriya Nurannisa Dewi ◽

Hajime Hisaeda ◽

Adrian L. Smith ◽

Fumiko Jimi ◽

...

Keyword(s):

Transforming Growth Factor ◽

Cell Monolayer ◽

Direct Interaction ◽

Intraepithelial Lymphocytes ◽

Epithelial Barrier ◽

Necrosis Factor Alpha ◽

Intestinal Intraepithelial Lymphocytes ◽

Tnf Α ◽

Ifn Γ ◽

Eimeria Vermiformis

ABSTRACT Eimeria spp. are intracellular protozoa that infect intestinal epithelia of most vertebrates, causing coccidiosis. Intestinal intraepithelial lymphocytes (IEL) that reside at the basolateral site of epithelial cells (EC) have immunoregulatory and immunoprotective roles against Eimeria spp. infection. However, it remains unknown how IEL are involved in the regulation of epithelial barrier during Eimeria sp. infection. Here, we demonstrated two distinct roles of IEL against infection with Eimeria vermiformis, a murine pathogen: production of cytokines to induce protective immunity and expression of junctional molecules to preserve epithelial barrier. The number of IEL markedly increased when oocyst production reached a peak. During infection, IEL increased production of gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α) and decreased transforming growth factor β (TGF-β) production. Addition of IFN-γ and TNF-α or supernatants obtained from cultured IEL from E. vermiformis-infected mice reduced transepithelial electrical resistance (TER) in a confluent CMT93 cell monolayer, a murine intestine-derived epithelial line, but antibodies against these cytokines suppressed the decline of TER. Moreover, TGF-β attenuated the damage of epithelial monolayer and changes in TER caused by IFN-γ and TNF-α. The expression of junctional molecules by EC was decreased when IEL produced a high level of IFN-γ and TNF-α and a low level of TGF-β in E. vermiformis-infected mice. Interestingly, IEL constantly expressed junctional molecules and a coculture of EC with IEL increased TER. These results suggest that IEL play important multifunctional roles not only in protection of the epithelium against E. vermiformis-induced change by cytokine production but also in direct interaction with the epithelial barrier when intra-EC junctions are down-regulated.

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Maternal Supplementation of Food Ingredient (Prebiotic) or Food Contaminant (Mycotoxin) Influences Mucosal Immune System in Piglets

Nutrients ◽

10.3390/nu12072115 ◽

2020 ◽

Vol 12 (7) ◽

pp. 2115

Author(s):

Stéphanie Ferret-Bernard ◽

Laurence Le Normand ◽

Véronique Romé ◽

Cindy Le Bourgot ◽

Julie Seeboth ◽

...

Keyword(s):

Immune System ◽

Lamina Propria ◽

Inflammatory Responses ◽

Intestinal Barrier ◽

Mucosal Immune System ◽

Food Ingredient ◽

Intestinal Immune System ◽

Maternal Supplementation ◽

Antigen Presenting ◽

The Impact

The early life period is crucial for the maturation of the intestinal barrier, its immune system, and a life-long beneficial host–microbiota interaction. The study aims to assess the impact of a beneficial dietary (short-chain fructooligosaccharides, scFOS) supplementation vs. a detrimental dietary environment (such as mycotoxin deoxynivalenol, DON) on offspring intestinal immune system developmental profiles. Sows were given scFOS-supplemented or DON-contaminated diets during the last 4 weeks of gestation, whereas force-feeding piglets with DON was performed during the first week of offspring life. Intestinal antigen-presenting cell (APC) subset frequency was analyzed by flow cytometry in the Peyer’s patches and in lamina propria and the responsiveness of intestinal explants to toll-like receptor (TLR) ligands was performed using ELISA and qRT-PCR from post-natal day (PND) 10 until PND90. Perinatal exposure with scFOS did not affect the ontogenesis of APC. While it early induced inflammatory responses in piglets, scFOS further promoted the T regulatory response after TLR activation. Sow and piglet DON contamination decreased CD16+ MHCII+ APC at PND10 in lamina propria associated with IFNγ inflammation and impairment of Treg response. Our study demonstrated that maternal prebiotic supplementation and mycotoxin contamination can modulate the mucosal immune system responsiveness of offspring through different pathways.

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Mesenchymal stromal cell plasticity and the tumor microenvironment

Emerging Topics in Life Sciences ◽

10.1042/etls20170141 ◽

2017 ◽

Vol 1 (5) ◽

pp. 487-492

Author(s):

Hee Joon Bae ◽

Shutong Liu ◽

Ping Jin ◽

David Stroncek

Keyword(s):

Tumor Microenvironment ◽

Transforming Growth Factor ◽

Critical Role ◽

Tumor Infiltrating Lymphocytes ◽

Transforming Growth Factor Β ◽

Interferon Γ ◽

Tnf Α ◽

Ifn Γ ◽

Factor Α ◽

Infiltrating Lymphocytes

Mesenchymal stem cells or mesenchymal stromal cells (MSCs) are a multipotent, heterogeneous population of cells that play a critical role in wound healing and tissue regeneration. MSCs, found in the tumor microenvironment, support tumor growth through the production of angiogenic factors, growth factors and extracellular matrix proteins. They also have immunomodulatory properties, and since they produce indoleamine 2,3-dioxygenase (IDO), prostaglandin E2 (PGE2) and transforming growth factor β (TGF-β), they have been thought to have primarily immunosuppressive effects. However, their role in the tumor microenvironment is complex and demonstrates plasticity depending on location, stimulatory factors and environment. The presence of melanoma-activated tumor-infiltrating lymphocytes (TILs) has been shown to produce pro-inflammatory changes with TH1 (type 1T helper)-like phenotype in MSCs via activated-TIL released cytokines such as interferon γ (IFN-γ), tumor necrosis factor α (TNF-α) and interleukin-1α (IL-1α), while simultaneously producing factors, such as IDO1, which have been traditionally associated with immunosuppression. Similarly, the combination of IFN-γ and TNF-α polarizes MSCs to a primarily TH1-like phenotype with the expression of immunosuppressive factors. Ultimately, further studies are encouraged and needed for a greater understanding of the role of MSCs in the tumor microenvironment and to improve cancer immunotherapy.

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Lack of Association between Cytokine Genetic Polymorphisms in Takayasu’s Arteritis in Mexican Patients

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph16234863 ◽

2019 ◽

Vol 16 (23) ◽

pp. 4863

Author(s):

María Elena Soto ◽

Claudia Huesca-Gómez ◽

Yazmín Torres-Paz ◽

Giovanny Fuentevilla-Álvarez ◽

Ricardo Gamboa

Keyword(s):

Transforming Growth Factor ◽

Takayasu’S Arteritis ◽

Interleukin 10 ◽

Mexican Population ◽

Takayasu's Arteritis ◽

American College Of Rheumatology ◽

Tnf Α ◽

Ifn Γ ◽

Necrosis Factor ◽

Control Study

Aim: To investigate the relation between polymorphisms in the interleukin 10 (IL)-10, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β and interferon (IFN)-γ genes and Takayasu’s arteritis in the Mexican population. Methods: A case-control study was performed to investigate the associations of IL-10, TNF-α, TGF-β and IFN-γ polymorphisms in a sample of 52 Takayasu’s arteritis patients, diagnosed according to the criteria of the American College of Rheumatology and EULAR PRINTO criteria when the patients were under 18 years of age; 60 clinically healthy unrelated Mexican individuals by the 5′ exonuclease TaqMan polymerase chain reaction. Polymorphic haplotypes were constructed after linkage disequilibrium analysis. Results: Significant differences were not found in the distribution for genotype and allele frequencies of the polymorphisms studied between healthy controls and Takayasu´s arteritis patients. Likewise, significant associations were not detected in the haplotype analysis with the different genes studied. Conclusions: These findings suggest that the polymorphisms in IL-10, TNF-α, TGF-β and IFN-γ might not contribute to the susceptibility of Takayasu´s arteritis in the Mexican population.

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Cytokine Gene Expression in Nasal Polyps

Annals of Otology Rhinology & Laryngology ◽

10.1177/000348949810700807 ◽

1998 ◽

Vol 107 (8) ◽

pp. 665-670 ◽

Cited By ~ 40

Author(s):

Chul Hee Lee ◽

Chae-Seo Rhee ◽

Yang-Gi Min

Keyword(s):

Gene Expression ◽

Southern Blot ◽

Nasal Polyp ◽

Nasal Polyps ◽

Transforming Growth Factor ◽

Cytokine Gene Expression ◽

Messenger Rnas ◽

Gene Expressions ◽

Ifn Γ ◽

Density Ratios

Nasal polyps are the most common mass lesion of the nasal cavity. Various pathogenetic mechanisms have been proposed. However, the cause is still largely unknown, and treatment methods have not been changed for several hundred years. In order to investigate the role of cytokines in the pathogenesis of nasal polyps, expression of cytokine messenger RNAs (mRNAs) in nasal polyps was investigated. We performed reverse transcriptase-polymerase chain reaction and Southern blot to examine gene expression of the cytokines interleukin (IL)-1ß, IL-6, IL-8, transforming growth factor (TGF)-ß, IL-4, IL-5, and interferon (IFN)-Γ and compared the results with the gene expressions of these cytokines in normal nasal mucosa. Nasal polyp tissues were obtained from 14 patients undergoing polypectomy for nasal obstruction. Among them, 4 patients suffered from associated perennial allergic rhinitis. The mRNAs of IL-4 and IL-5 (Th2 cytokines) as well as IFN-γ (Thl cytokine) were expressed in all of the nasal polyps obtained from the 14 patients, irrespective of the presence or absence of allergy, while 2, 0, and 4 of 6 normal turbinate mucosae expressed IL-4, IL-5, and IFN-γ mRNAs, respectively. The mRNAs of IL-1ß, IL-6, IL-8, and TGF-ß were expressed in 6, 1, 2, and 3 of 6 normal turbinate mucosae, respectively, while the mRNAs of these cytokines were expressed in all of the 14 polyp tissues except IL-6 mRNA, which was expressed in 13 nasal polyp tissues. There were no differences in the mean density ratios of each cytokine band on Southern blot between polyp tissues with allergy and those without allergy. These results suggest that many cytokines are produced in nasal polyps, that they may play important roles in the pathogenesis of nasal polyps, and that allergy per se may not play a fundamental role in the pathogenesis of nasal polyps.

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Increased Expression of TLR2 and TLR4 in Mononuclear Cells in Patient with Immune Thrombocytopenic Purpura.

Blood ◽

10.1182/blood.v110.11.3847.3847 ◽

2007 ◽

Vol 110 (11) ◽

pp. 3847-3847 ◽

Cited By ~ 1

Author(s):

Yunfeng Cheng ◽

Shanhua Zou ◽

Feng Li

Keyword(s):

Plasma Concentration ◽

Mrna Expression ◽

Mononuclear Cells ◽

Control Group ◽

Gene Expressions ◽

Expression Levels ◽

Tnf Α ◽

Healthy Control ◽

Ifn Γ ◽

Mrna Expression Levels

Abstract Immune thrombocytopenic purpura (ITP) is an autoimmune disease characterized by platelet destruction resulting from autoantibodies against self-antigens and T-cell mediated cytotoxicity. Toll-like receptors (TLRs) are pattern recognition receptors important in mediating the immune response and their activation can lead to production of cytokines. Recent data suggest that TLR2 and TLR4 are crucial for the production of inflammatory cytokines and play central role in autoimmune diseases, yet little is known about their roles in ITP. Here we examined the gene expressions of TLR2 and TLR4 in ITP patients. We hypothesize that significant differences will exist between pre-treatment and post-treatment in ITP patients with similar changes reflected in the plasma concentration of cytokines. Total RNA was extracted from mononuclear cells obtained from 12 ITP patients and 15 healthy subjects. TLR2 and TLR4 mRNA expression levels were analyzed using a quantitative real-time PCR method and their protein expressions were validated by western blot. Plasma concentrations of cytokines IL-2, IFN-γ and TNF-α were measured by ELISA. Correlation analyses were carried out between the mRNA expression levels of TLR2 or TLR4 and the plasma levels of IL-2, IFN-γ and TNF-α. The gene expression of TLR2 and TLR4 were significantly increased in ITP patients comparing to healthy control group (p < 0.05 and p < 0.01, respectively). In addition their mRNA expression levels were decreased back into normal range after remission in 8 patients (p > 0.05, compared to healthy control group). Significantly positive correlations were found between the TLR2 mRNA expression level and the plasma concentration of IFN-γ or TNF-α (R = 0.75, p < 0.05; R = 0.83, p < 0.05, respectively). Changes in the gene expression of TLR4 and in the plasma concentration of IFN-γ or TNF-α were also significantly correlated (R = 0.82, p < 0.05; R = 0.88, p < 0.05, respectively). Directional changes in TLR2 / TLR4 and IFN-γ /TNF-α expression were concordant. However, there was no correlation found between TLR2 / TLR4 and IL-2. Differences in TLR2 and TLR4 expression strongly correlated with changes in IFN-γ and TNF-α suggest that the increased gene expressions of TLR2 and TLR4 in ITP patients may contribute to the pathophysiological progression of this disease by increasing the secretion of IFN-γ and TNF-α. Additional studies need to be performed to further clarify the role of TLRs -cytokines pathway in ITP.

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Production and Expression of Inflammatory Mediators in Leukocytes of Sickle Cell Anaemia Patients and Effects of Hydroxyurea Therapy on This Production

Blood ◽

10.1182/blood.v112.11.2490.2490 ◽

2008 ◽

Vol 112 (11) ◽

pp. 2490-2490

Author(s):

Carolina Lanaro ◽

Carla Fernanda Franco-Penteado ◽

Dulcinéia M Albuquerque ◽

Sara T.O. Saad ◽

Nicola Conran ◽

...

Keyword(s):

Steady State ◽

Sickle Cell ◽

Inflammatory Mediators ◽

Healthy Controls ◽

Gene Expressions ◽

Tnf Α ◽

Ifn Γ ◽

Cox 2 ◽

Anti Inflammatory ◽

Hydroxyurea Therapy

Abstract Leukocytosis is frequently observed in sickle cell disease (SCD) in the absence of bacterial infection. An elevated baseline leukocyte count is associated with an increased risk of early death and leukocytes play a significant role in the initiation of vaso-occlusive events. Inflammation, cell adhesion to vascular endothelium, and subsequent endothelial injury appear to contribute to sickle cell anemia (SCA) vaso-occlusion. Furthermore, blood levels of inflammatory and anti-inflammatory cytokines are reported to be elevated (TNF-α, IL-6, IL-10, GM-CSF), both in steady state and during crisis, but reports have been conflicting and a conclusive role for these molecules in the disease remains to be established. Furthermore, the effect of hydroxyurea therapy (HU) on the release of inflammatory mediators is not understood. The aim of this study was to determine plasma levels and leukocyte gene expressions of inflammatory mediators in healthy controls (n=30), steady-state SCA patients (n=45) and SCA patients on HU therapy (n=24). qRT-PCR analysis was use to examine gene expression and ELISA protein production. TNF-α, IL-8 and PGE2 plasma levels were significantly higher in the plasma of steady-state SCA individuals, when compared to control individuals (2.95 ± 0.4 pg/ml; 16.5 ± 2.5 pg/ml; 5.7 ± 0.6 pg/ml; 128.3 ± 12.2 pg/ml vs 1.43 ± 0.2 pg/ml, 88.5 ± 5.9 pg/ml, P=0.006; P<0.0001; P=0.012, respectively). HU therapy significantly reversed augmented TNF-α (1.6 ± 0.2 pg/ml, P=0.006) and, interestingly, increased plasma anti-inflammatory IL-10 (P<0.05). IL-10, IFN-γ, COX-2 and iNOS gene expressions were unaltered in SCA mononuclear cells (MC), however gene expressions of TNF-α, IL-8 and the protective enzyme, heme oxygenase-1 (HO-1), were significantly higher compared to healthy controls (0.46 ± 0.01; 0.08 ± 0.02; 0.21 ± 0.05 vs 0.18 ± 0.04; 0.02 ± 0.005; 0.035 ± 0.008; respectively, P<0.02). HU therapy was not associated with significantly altered SCA MC inflammatory gene expression, although COX-2 mRNA expression was decreased (0.11 ± 0.05; 0.37 ± 0.12, SCAHU and SCA, respectively; P<0.05). In SCA neutrophils, gene expressions of IL-8, IFN-γ, iNOS and HO-1 were significantly higher compared to those of control subjects (0.32 ± 0.07; 0.69 ± 0.19; 0.19 ± 0.06; 0.33 ± 0.09, P=0.02, P=0.025, P<0.05; P=0.027, respectively). Patients on HU therapy demonstrated lower iNOS and higher IL-10 neutrophil gene expressions compared to SCA not on HU therapy (0.038 ± 0.03; 0.72 ± 0.13, P<0.05; P<0.05, respectively). Taken together, data suggest that alterations in the gene expressions and productions of a number of pro-and anti-inflammatory mediators are present in SCA and knowledge of these pathways may be important for identifying novel drug targets for the disease.

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Immunogenomic signatures to predict outcome in ovarian and endometrial cancers: Potential strategies in targeting the tumor immune microenvironment to improve response to immunotherapy.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.5_suppl.4 ◽

2020 ◽

Vol 38 (5_suppl) ◽

pp. 4-4

Author(s):

Haider Mahdi ◽

Ying Ni

Keyword(s):

Endometrial Cancer ◽

Immune Cells ◽

Transforming Growth Factor ◽

Immune Cell ◽

Checkpoint Inhibitors ◽

Individual Gene ◽

Cell Abundance ◽

Ifn Γ ◽

Endometrial Cancers ◽

The Impact

4 Background: Ovarian and MSS endometrial cancers are characterized by immunosuppressive microenvironment (TME) and low response to immunotherapy with checkpoint inhibitors (CPI). Targeting immunosuppressive factors within TMErepresents an attractive approach to enhance response to CPI. Therefore, we sought to investigate different immunogenomic signatures and immune cells within TME and correlate them with survival. Methods: We used whole transcriptome sequencing of matched tumor-normal samples from 38 uterine serous cancer and TCGA data of ovarian (n = 374) and endometrial cancers (n = 541). Immunogenomic signatures focusing on Transforming Growth Factor (TGFβ), 18-genes IFN-γ and myeloid signatures (CD47 and B7H4 expressions) and immune cell abundance were investigated. Gene expression score was calculated by averaging the normalized and log transformed individual gene read counts. The optimized score cut off was selected to best separate the survival in the pilot cohort. Then the score was tested in TCGA RNAseq datasets. Population abundance of tissue-infiltrating immune cells were estimated using MCPcounter R package from bulk transcriptome data. Results: Higher IFN-γ and lower TGF-β signatures predicted better survival for endometrial and ovarian cancers (p < 0.05). The impact of TGF-β was higher in MSI-H vs. MSS cancers (p = 0.013 vs. 0.09). High CD47 predicted poor survival in endometrial cancer. Combined IFN-γ and TGF-β signatures predicted survival in the ovarian and endometrial cohorts (p < 0.001). Combined IFN-γ and CD47 expression predicted survival in endometrial cancer (p = 0.033). Analysis of immune cell abundance revealed enrichment of monocytic lineage and neutrophils but paucity of cytotoxic T-cells, NK cells, dendritic cells and B-cells. Immune cell abundance is being correlated with survival. Conclusions: Our data support the role of immunogenomic markers in predicting survival. We are evaluating these markers in predicting response to CPI in a pilot cohort. Immunogenomic markers represent the tumor microenvironment, can potentially guide rationale combination immunotherapy.

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