The role of IL-7 in Immunity and Cancer

doi:10.21873/anticanres.11405

Cited by 94 publications

(48 citation statements)

References 29 publications

(35 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The only significantly increased cytokine during G19 VSG pregnancy was interleukin 7. IL7 can be released with immune activation of the gut (31, 32) and globally works to increase maturation of T cells when lymphopenia is present (18). We hypothesized that IL7 may be increased to compensate for the reduced number of total T cells, especially cytotoxic T cells, in the cell sorting experiments.…”

Section: Discussionmentioning

confidence: 99%

Rodent vertical sleeve gastrectomy alters maternal immune health and fetoplacental development

et al. 2018

View full text Add to dashboard Cite

Bariatric surgery is increasingly employed to improve fertility and reduce obesity related co-morbidities in obese women. Surgical weight loss not only improves the chance of conception but reduces the risk of pregnancy complications including pre-eclampsia, gestational diabetes, and macrosomia. However, bariatric procedures increase the incidence of intrauterine growth restriction (IUGR), fetal demise, thromboembolism and other gestational disorders. Using our rodent model of vertical sleeve gastrectomy (VSG), we tested the hypothesis that VSG in diet-induced, obese dams would cause immune and placental structural abnormalities that may be responsible for fetal demise during pregnancy. VSG dams studied on gestational day (G) 19 had reduced circulating T cell (CD3+ and CD8+) populations compared to lean or obese controls. Further, local interleukin 1 β and interleukin 1 receptor antagonist mRNA were increased in placenta of VSG dams. Placental barrier function was also affected, with increased trans-placental permeability to small molecules, increased matrix metalloproteinase 9 expression, and increased apoptosis in VSG. Furthermore, we identified increased placental mTOR signaling that may contribute to preserving the body weight of the fetuses during gestation. These changes occurred in the absence of a macronutrient deficit or gestational hypertension in the VSG dams. In summary, previous VSG in dams may contribute to fetal demise by affecting maternal immune system activity and compromise placental integrity.

show abstract

Section: Discussionmentioning

confidence: 99%

Rodent vertical sleeve gastrectomy alters maternal immune health and fetoplacental development

et al. 2018

View full text Add to dashboard Cite

show abstract

“…A possible mechanism for this is that the destruction of the local immunosuppressive microenvironment contributes to tumor antigen presentation and consequently activates multiple antigen-specific effector T cells which are capable of specifically attacking tumor cells at any sites in the body when combined with anti-PD-1 therapy. AGT silencing in hypoxic 4T1 cells triggered an immune-activating cytokine profile, including some cytokines involved in attracting, activating, and stimulating proliferation of dendritic cells and T cells [ 43 – 49 ], which contributes to tumor antigen presentation and generation of multiple tumor-antigen-specific effector T cells. Therefore, the altered immune microenvironment in a local tumor by AGT expression-silencing may elicit an in situ tumor vaccination and generate productive tumor-specific T cells to achieve a systemic in vivo anti-tumor effect.…”

Section: Discussionmentioning

confidence: 99%

Local angiotensin II contributes to tumor resistance to checkpoint immunotherapy

Xie¹,

Cheng²,

Lin³

et al. 2018

j. immunotherapy cancer

View full text Add to dashboard Cite

BackgroundCurrent checkpoint immunotherapy has shown potential to control cancer by restoring or activating the immune system. Nevertheless, multiple mechanisms are involved in immunotherapy resistance which limits the clinical benefit of checkpoint inhibitors. An immunosuppressive microenvironment is an important factor mediating the original resistance of tumors to immunotherapy. A previous report by our group has demonstrated that local angiotensin II (AngII) predominantly exists in a tumor hypoxic microenvironment where hypoxic tumour cells produced AngII by a hypoxia-lactate-chymase-dependent mechanism.ResultsHere, using 4T1 and CT26 syngeneic mouse tumor models, we found that local AngII in the tumor microenvironment was involved in immune escape of tumour cells and an AngII signaling blockage sensitized tumours to checkpoint immunotherapy. Furthermore, an AngII signaling blockage reversed the tumor immunosuppressive microenvironment, and inhibition of angiotensinogen (AGT, a precursor of AngII) expression strongly triggered an immune-activating cytokine profile in hypoxic mouse cancer cells. More importantly, AGT silencing combined with a checkpoint blockage generated an abscopal effect in resistant tumors.ConclusionOur study demonstrated an important role of local AngII in the formation of a tumor immunosuppressive microenvironment and its blockage may enhance tumor sensitivity to checkpoint immunotherapy. The combination of an AngII signaling blocker and an immune-checkpoint blockage could be a promising strategy to improve tumors responses to current checkpoint immunotherapy.Electronic supplementary materialThe online version of this article (10.1186/s40425-018-0401-3) contains supplementary material, which is available to authorized users.

show abstract

“…Also correlating were GZMB and FASLG , both necessary for anti-tumor CD8 T cell cytotoxic functionality [ 49 ], PD-1 and LAG3 , representing T cell activation and exhaustion [ 50 ], and TAP2 , necessary in MHC I antigen presentation [ 51 ]. Cytokines inversely correlating with neo-antigen burden included TSLP and IL33 , involved in the Th2 response [ 52 ], IL7 , implicated with pro- and anti-tumorigenic properties [ 53 ], EDA2R , which is involved in p53 signaling [ 53 ], and multiple genes in the TRAIL apoptosis pathway. Additionally, neo-antigen load correlated with increased expression of the chemokines TNFRSF25 , CCR1 , and LTBR , which may serve as valuable targets in future tumor immunology studies (Figure 5A ).…”

Section: Discussionmentioning

confidence: 99%

Mutations in DNA repair genes are associated with increased neo-antigen load and activated T cell infiltration in lung adenocarcinoma

et al. 2017

View full text Add to dashboard Cite

Mutations in DNA repair genes lead to increased genomic instability and mutation frequency. These mutations represent potential biomarkers for cancer immunotherapy efficacy, as high tumor mutational burden has been associated with increased neo-antigens and tumor infiltrating lymphocytes. While mismatch repair mutations have successfully predicted response to anti-PD-1 therapy in colorectal and other cancers, they have not yet been tested for lung cancer, and few have investigated genes from other DNA repair pathways. We utilized TCGA samples to comprehensively immunophenotype lung tumors and analyze the links between DNA repair mutations, neo-antigen and total mutational burden, and tumor immune infiltration. Overall, 73% of lung tumors contained infiltration by at least one T cell subset, with high mutational burden tumors containing significantly increased infiltration by activated CD4 and CD8 T cells. Further, mutations in mismatch repair genes, homologous recombination genes, or POLE accurately predicted increased tumor mutational burden, neo-antigen load, and T cell infiltration. Finally, neo-antigen load correlated with expression of M1-polarized macrophage genes, PD-1, PD-L1, IFNγ, GZMB, and FASLG, among other immune-related genes. Overall, after defining the immune infiltrate in lung tumors, we demonstrate the potential value of utilizing gene mutations from multiple DNA repair pathways as biomarkers for lung cancer immunotherapy.

show abstract

The role of IL-7 in Immunity and Cancer

Cited by 94 publications

References 29 publications

Rodent vertical sleeve gastrectomy alters maternal immune health and fetoplacental development

Rodent vertical sleeve gastrectomy alters maternal immune health and fetoplacental development

Local angiotensin II contributes to tumor resistance to checkpoint immunotherapy

Mutations in DNA repair genes are associated with increased neo-antigen load and activated T cell infiltration in lung adenocarcinoma

Contact Info

Product

Resources

About