Thymic Stromal Lymphopoietin Induction Suppresses Lung Cancer Development

Abstract

Lung cancer is the leading cause of cancer deaths in the United States and across the world. Immunotherapies, which activate tumor-infiltrating cytotoxic T lymphocytes, have demonstrated efficacy for the treatment of advanced-stage lung cancer. However, the potential for harnessing the immune system against the early stages of lung carcinogenesis to prevent cancer development and recurrence remains unexplored. Using a mouse model of lung adenocarcinoma, we investigated the effects of thymic stromal lymphopoietin (TSLP) induction on early cancer development in the lungs. Herein, we demonstrate that systemic TSLP induction suppressed spontaneous lung cancer development in KrasG12D mice. TSLP drove a significant CD4+ T cell response to block lung cancer progression from atypical alveolar hyperplasia to adenocarcinoma. Our findings suggest that TSLP can be used in the early stages of lung cancer development to trigger a lasting immunity in the tissue and prevent the development of advanced disease.

BAMBI: Integrativebiostatistical andartificial-intelligencemodels discover coding and non-coding RNA genes asbiomarkers

“…(D) Known functional roles of the putative coding gene biomarkers (TSLP and SPRY2) in breast cancer. TSLP were shown to inhibit the breast tumorigenesis through Th2 (Boieri et al, 2022; Demehri et al, 2016b; Guennoun et al, 2022), and the repressing the expression of SPRY2 would lead to promote the breast cancer progression through the hyperactivation of the Ras/Raf/ERK pathway (Faratian et al, 2011; Hanafusa et al, 2002; Kawazoe & Taniguchi, 2019). (E-G) The five putative lncRNA-biomarkers are contained in three co-expression clusters (Cluster I, II and III).…”

“…The five lncRNA biomarkers are coexpressed with three groups of coding-genes (Fig 2E and F). Among these five lncRNA biomarkers: 1) the HSALNG002284 was co-expressed with coding genes involved in extracellular matrix structural constituent, collagen binding and integrin binding ( (Boieri et al, 2022;Demehri et al, 2016b;Guennoun et al, 2022), and the repressing the expression of SPRY2 would lead to promote the breast cancer progression through the hyperactivation of the Ras/Raf/ERK pathway (Faratian et al, 2011;Hanafusa et al, 2002;Kawazoe & Taniguchi, 2019).…”

The causal effect of atopic dermatitis on lung cancer: A Mendelian randomization study

“…51 Systemic TSLP induction has driven a significant Th2 immunity to prevent tumorigenesis progression from atypical alveolar hyperplasia to LUAD. 52 Moreover, serum IgE levels may be related to antitumor response in patients with atopic diseases. IgE plays an essential role in triggering immune responses to cancer cells, such as in the pancreas, colon, and rectum.…”

“…TSLP is an efficient activator of dendritic cells that promotes Th2‐mediated immune response 51 . Systemic TSLP induction has driven a significant Th2 immunity to prevent tumorigenesis progression from atypical alveolar hyperplasia to LUAD 52 . Moreover, serum IgE levels may be related to antitumor response in patients with atopic diseases.…”