Interleukin-38 promotes tumor growth through regulation of CD8+ tumor-infiltrating lymphocytes in lung cancer tumor microenvironment

Kinoshita, Fumihiko; Tagawa, Tetsuzo; Akamine, Takaki; Takada, Kazuki; Yamada, Yuichi; Oku, Yuka; Kosai, Keisuke; Ono, Yuki; Tanaka, Kensuke; Wakasu, Sho; Oba, Taro; Osoegawa, Atsushi; Shimokawa, Mototsugu; Oda, Yoshinao; Hoshino, Tomoaki; Mori, Masaki

doi:10.1007/s00262-020-02659-9

Cited by 27 publications

(19 citation statements)

References 26 publications

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“…Results from another newly conducted study by Fumihiko Kinoshita et al [190] that aimed at investigating the association of IL-38 and tumor growth in the microenvironment of lung cancer demonstrated a correlation between higher concentrations of IL-38 and poor prognosis in lung adenocarcinoma. In their experimental study, they established IL-38-plasmid-transfected Lewis lung carcinoma cells (LLC-IL-38), and CD8 + lymphocyte depletion models to examine possible relationships between the concentrations of IL-38 and CD8 + lymphocytes.…”

Section: Lung Adenocarcinomamentioning

confidence: 99%

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Immunobiological Properties and Clinical Applications of Interleukin-38 for Immune-Mediated Disorders: A Systematic Review Study

Esmaeilzadeh

Bahmaie

Nouri

et al. 2021

IJMS

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Exponential growth in the usage of “cytokines” (as seroimmunobiomarkers) has facilitated more accurate prognosis, early diagnosis, novel, and efficient immunotherapeutics. Numerous studies have reported immunopathophysiological and immunopathological processes of interleukin-38 (IL-38). Therefore, in this systematic review article, the authors aimed to present an updated comprehensive overview on the immunobiological mechanisms, diagnostic, and immune gene-based therapeutic potentials of IL-38. According to our inclusion and exclusion criteria, a total of 216 articles were collected from several search engines and databases from the January 2012 to July 2021 time interval by using six main keywords. Physiologic or pathologic microenvironments, optimal dosage, and involved receptors affect the functionalities of IL-38. Alterations in serum levels of IL-38 play a major role in the immunopathogenesis of a wide array of immune-mediated disorders. IL-38 shows anti-inflammatory activities by reduction or inhibition of pro-inflammatory cytokines, supporting the therapeutic aspects of IL-38 in inflammatory autoimmune diseases. According to the importance of pre-clinical studies, it seems that manipulation of the immune system by immunomodulatory properties of IL-38 can increase the accuracy of diagnosis, and decipher optimal clinical outcomes. To promote our knowledge, more collaboration is highly recommended among laboratory scientists, internal/infectious diseases specialists, oncologists, immunologists, diseases-specific biomarkers scientists, and basic medical researchers.

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Section: Lung Adenocarcinomamentioning

confidence: 99%

“…Thereafter, they reported that there was an inverse relationship between the expression of IL-38 in cancerous cells and tumor-infiltrating CD8 + lymphocytes in lung tumor progression. Therefore, IL-38 can be promisingly recruited as a screening seroimmunobiomarker and a targeted immunotherapeutic approach for lung tumors [190].…”

Section: Lung Adenocarcinomamentioning

confidence: 99%

Immunobiological Properties and Clinical Applications of Interleukin-38 for Immune-Mediated Disorders: A Systematic Review Study

Esmaeilzadeh

Bahmaie

Nouri

et al. 2021

IJMS

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“…There are many immune cells and signaling pathways in mechanism that may regulate the diseases progression via IL-38. For instance, IL-38 can promote tumor growth in lung cancer tumor microenvironment via regulating CD8 + tumor-infiltrating lymphocytes ( Kinoshita et al, 2021 ). It suggested that IL-38 may participate in lung cancer by regulating immune cells.…”

Section: Overview Of Il-38mentioning

confidence: 99%

The Pathological Mechanism and Potential Application of IL-38 in Autoimmune Diseases

et al. 2021

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Interleukin-38 (IL-38), a new cytokine of interleukin-1 family (IL-1F), is expressed in the human heart, kidney, skin, etc. Recently, new evidence indicated that IL-38 is involved in the process of different autoimmune diseases. Autoimmune diseases are a cluster of diseases accompanied with tissue damage caused by autoimmune reactions, including rheumatoid arthritis (RA), psoriasis, etc. This review summarized the links between IL-38 and autoimmune diseases, as well as the latest knowledge about the function and regulatory mechanism of IL-38 in autoimmune diseases. Especially, this review focused on the differentiation of immune cells and explore future prospects, such as the application of IL-38 in new technologies. Understanding the function of IL-38 is helpful to shed light on the progress of autoimmune diseases.

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“…For instance, CD8-positive (CD8+) tumor-infiltrating lymphocytes (TILs) in the peri-tumoral microenvironment are significantly correlated with poor clinical outcome of salivary gland carcinoma patients ( Kesar et al, 2020 ). Mechanically, interleukin-38 advances tumor growth by affecting CD8 + TILs in the TME of lung cancer ( Kinoshita et al, 2020 ). In addition, dual suppression of both PI3K-γ and colony stimulating factor-1/colony stimulating factor-1 receptor (CSF-1/CSF-1R) pathways in tumor associated macrophages (TAM) could remodel tumor immune microenvironment (TIME) and synergistically activate antitumor immune responses in pancreatic cancer ( Li et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

TGFβ1: An Indicator for Tumor Immune Microenvironment of Colon Cancer From a Comprehensive Analysis of TCGA

Wang

Wang²,

et al. 2021

Front. Genet.

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BackgroundTumor microenvironment (TME) and tumor-infiltrating immune cells (TICs) greatly participate in the genesis and development of colon cancer (CC). However, there is little research exploring the dynamic modulation of TME.MethodsWe analyzed the proportion of immune/stromal component and TICs in the TME of 473 CC samples and 41 normal samples from The Cancer Genome Atlas (TCGA) database through ESTIMATE and CIBERSORT algorithms. Correlation analysis was conducted to evaluate the association between immune/stromal component in the TME and clinicopathological characteristics of CC patients. The difference analysis was performed to obtain the differentially expressed genes (DEGs). These DEGs were further analyzed by GO and KEGG enrichment analyses, PPI network, and COX regression analysis. Transforming growth factor β1 (TGFβ1) was finally overlapped from the above analysis. Paired analysis and GSEA were carried out to understand the role of TGFβ1 in colon cancer. The intersection between the difference analysis and correlation analysis was conducted to learn the association between TGFβ1 and TICs.ResultsOur results showed that the immune component in the TME was negatively related with the stages of CC. GO and KEGG enrichment analysis revealed that 1,110 DEGs obtained from the difference analysis were mainly enriched in immune-related activities. The intersection analysis between PPI network and COX regression analysis indicated that TGFβ1 was significantly associated with the communication of genes in the PPI network and the survival of CC patients. In addition, TGFβ1 was up-regulated in the tumor samples and significantly related with poor prognosis of CC patients. Further GSEA suggested that genes in the TGFβ1 up-regulated group were enriched in immune-related activities and the function of TGFβ1 might depend on the communications with TICs, including T cells CD4 naïve and T cells regulatory.ConclusionThe expression of TGFβ1 might be an indicator for the tumor immune microenvironment of CC and serve as a prognostic factor. Drugs targeting TGFβ1 might be a potential immunotherapy for CC patients in the future.

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Interleukin-38 promotes tumor growth through regulation of CD8+ tumor-infiltrating lymphocytes in lung cancer tumor microenvironment

Cited by 27 publications

References 26 publications

Immunobiological Properties and Clinical Applications of Interleukin-38 for Immune-Mediated Disorders: A Systematic Review Study

Immunobiological Properties and Clinical Applications of Interleukin-38 for Immune-Mediated Disorders: A Systematic Review Study

The Pathological Mechanism and Potential Application of IL-38 in Autoimmune Diseases

TGFβ1: An Indicator for Tumor Immune Microenvironment of Colon Cancer From a Comprehensive Analysis of TCGA

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