Interleukin-1β provided by KIT-competent mast cells is required for <i>KRAS</i>-mutant lung adenocarcinoma

Lilis, Ioannis; Ntaliarda, Giannoula; Papaleonidopoulos, Vassilios; Giotopoulou, Georgia A.; Oplopoiou, Maria; Marazioti, Antonia; Spella, Magda; Marwitz, Sebastian; Goldmann, Torsten; Bravou, Vasiliki; Giopanou, Ioanna; Stathopoulos, Georgios T.

doi:10.1080/2162402x.2019.1593802

Cited by 15 publications

(14 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Two external cohorts confirmed this conclusion. The differences and controversial conclusions in different studies (Baram et al , 2001; Kurebayashi et al , 2016; Lilis et al , 2019) may be due to the mixture of activated and resting mast cells. The function of activated mast cells may be masked by the resting mast cells.…”

Section: Discussionmentioning

confidence: 97%

“…One study revealed that mast cells correlated with angiogenesis and poor outcome in stage I LUAD (Baram et al , 2001). Another study has revealed KIT‐competent mast cells fuel KRAS‐mutant LUAD formation, growth and metastasis by providing interleukin‐1β and are associated with LUAD progression (Lilis et al , 2019). However, one research indicated that only mast cells were found by univariate analysis to be associated with better prognosis in LUAD (Kurebayashi et al , 2016).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Mast cell‐based molecular subtypes and signature associated with clinical outcome in early‐stage lung adenocarcinoma

et al. 2020

View full text Add to dashboard Cite

Mast cells are a major component of the immune microenvironment in tumour tissues and modulate tumour progression by releasing pro-tumorigenic and antitumorigenic molecules. Regarding the impact of mast cells on the outcomes of patients with lung adenocarcinoma (LUAD) patient, several published studies have shown contradictory results. Here, we aimed at elucidating the role of mast cells in early-stage LUAD. We found that high mast cell abundance was correlated with prolonged survival in earlystage LUAD patients. The mast cell-related gene signature and gene mutation data sets were used to stratify early-stage LUAD patients into two molecular subtypes (subtype 1 and subtype 2). The neural network-based framework constructed with the mast cell-related signature showed high accuracy in predicting response to immunotherapy. Importantly, the prognostic mast cell-related signature predicted the survival probability and the potential relationship between TP53 mutation, c-MYC activation and mast cell activities. The meta-analysis confirmed the prognostic value of the mast cell-related gene signature. In summary, this study might improve our understanding of the role of mast cells in early-stage LUAD and aid in the development of immunotherapy and personalized treatments for early-stage LUAD patients.

show abstract

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Mast cell‐based molecular subtypes and signature associated with clinical outcome in early‐stage lung adenocarcinoma

et al. 2020

View full text Add to dashboard Cite

show abstract

“…84 Mast cells could facilitate growth and metastasis by generating IL-1β in LUAD progression. 85 Conversely, certain studies revealed that greater abundance of mast cells was related to better prognosis and prolonged survival in early-stage LUAD cases. 54,86 We also found relatively enhanced expression of CD4 and CD8A indicative of a strengthened immune response in the low-risk group.…”

Section: Discussionmentioning

confidence: 99%

Immune landscape and a promising immune prognostic model associated with TP53 in early‐stage lung adenocarcinoma

Xiang

Wei

2020

Cancer Medicine

View full text Add to dashboard Cite

Purpose TP53 mutation, one of the most frequent mutations in early‐stage lung adenocarcinoma (LUAD), triggers a series of alterations in the immune landscape, progression, and clinical outcome of early‐stage LUAD. Our study was designed to unravel the effects of TP53 mutation on the immunophenotype of early‐stage LUAD and formulate a TP53‐associated immune prognostic model (IPM) that can estimate prognosis in early‐stage LUAD patients. Materials and methods Immune‐associated differentially expressed genes (DEGs) between TP53 mutated (TP53MUT) and TP53 wild‐type (TP53WT) early‐stage LUAD were comprehensively analyzed. Univariate Cox analysis and least absolute shrinkage and selection operator (LASSO) analysis identified the prognostic immune‐associated DEGs. We constructed and validated an IPM based on the TCGA and a meta‐GEO composed of GSE72094, GSE42127, and GSE31210, respectively. The CIBERSORT algorithm was analyzed for assessing the percentage of immune cell types. A nomogram model was established for clinical application. Results TP53 mutation occurred in approximately 50.00% of LUAD patients, stimulating a weakened immune response in early‐stage LUAD. Sixty‐seven immune‐associated DEGs were determined between TP53WT and TP53MUT cohort. An IPM consisting of two prognostic immune‐associated DEGs (risk score = 0.098 * ENTPD2 expression + 0.168 * MIF expression) was developed through 397 cases in the TCGA and further validated based on 623 patients in a meta‐GEO. The IPM stratified patients into low or high risk of undesirable survival and was identified as an independent prognostic indicator in multivariate analysis (HR = 2.09, 95% CI: 1.43–3.06, p < 0.001). Increased expressions of PD‐L1, CTLA‐4, and TIGIT were revealed in the high‐risk group. Prognostic nomogram incorporating the IPM and other clinicopathological parameters (TNM stage and age) achieved optimal predictive accuracy and clinical utility. Conclusion The IPM based on TP53 status is a reliable and robust immune signature to identify early‐stage LUAD patients with high risk of unfavorable survival.

show abstract

“…Infiltration of MCs has also been reported in human lung adenocarcinoma (LADC) tissues. Lilis and coworkers applied three KRAS-mutant LADC models to two MC-deficient mouse strains (cKitWsh and Cpa3.Cre) [50]. Acts through CGRPR and induces serotonin release [67] They showed that MCs infiltrate into tumors and that a MC deficiency protects the mice from tumor initiation within the airway and alveolar epithelium following induction with the carcinogen urethane or the oncogenic KRASG12D mutant respectively.…”

Section: Role Of Mcs In Lung Cancermentioning

confidence: 99%

“…Acts through CGRPR and induces serotonin release [67] They showed that MCs infiltrate into tumors and that a MC deficiency protects the mice from tumor initiation within the airway and alveolar epithelium following induction with the carcinogen urethane or the oncogenic KRASG12D mutant respectively. Enhanced tumor progression required IL-1β release from KIT+ MCs localized within the TME [50].…”

Section: Role Of Mcs In Lung Cancermentioning

confidence: 99%

The Role of Mast Cells in IgE-Independent Lung Diseases

Komi

Mortaz

Amani

et al. 2020

Clinic Rev Allerg Immunol

View full text Add to dashboard Cite

Mast cells (MCs) are granular cells of the innate immune system which develop from CD34 + /CD117 + progenitors and play a role in orchestrating adaptive immune responses. They have a well-known role in allergic reactions following immunoglobulin (Ig)Emediated activation of the cell-surface expressed IgE high-affinity receptor (FcεRI). MCs can also respond to various other stimuli due to the expression of a variety of receptors including toll-like receptors (TLRs), immunoglobulin (IgG) receptors (FcγR), complement receptors such as C5a (CD88) expressed by skin MCs, neuropeptides receptors including nerve growth factor receptor, (NGFR), cytokines receptors such as (IL)-1R and IL-3R, and chemokines receptors including CCR-1 and CCR-3. MCs release three groups of mediators upon degranulation differentiated according to their chemical composition, storage, and time to release. These include preformed mediators (mainly histamine, tryptase, and chymase), de novo synthesized mediators such as prostaglandin (PG)D2, leukotriene (LT)B4 and LTD4, and cytokines including IL-1β, IL-3, tumor necrosis factor (TNF)α, and transforming growth factor(TGF)-β. Emerging evidence indicates a role for IgE-independent MC activation in the late-stage asthmatic response as well as in non-allergic airway diseases including chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and lung cancer. MC infiltration/activation has been reported in some, but not all, studies of lung cancer. MC-derived TNF-α possesses tumor-suppressive activity while IL-1β supports tumor progression and metastasis. In IPF lungs, an increase in density of tryptase-and chymase-positive MCs (MCTC) and overexpression of TGF-β support the fibrosis progression. MC-derived chymase activates latent TGF-β that induces the differentiation of fibroblasts to matrix-producing myofibroblasts. In summary, increasing evidence highlights a critical role of MCs in non-allergic diseases that may indicate new approaches for therapy.

show abstract

Interleukin-1β provided by KIT-competent mast cells is required for KRAS-mutant lung adenocarcinoma

Cited by 15 publications

References 66 publications

Mast cell‐based molecular subtypes and signature associated with clinical outcome in early‐stage lung adenocarcinoma

Mast cell‐based molecular subtypes and signature associated with clinical outcome in early‐stage lung adenocarcinoma

Immune landscape and a promising immune prognostic model associated with TP53 in early‐stage lung adenocarcinoma

The Role of Mast Cells in IgE-Independent Lung Diseases

Contact Info

Product

Resources

About