Expression of the chemokine receptor CCR6 correlates with a favorable prognosis in patients with adenocarcinoma of the lung

Minamiya, Yoshihiro; Saito, Hajime; Takahashi, Naoko; Ito, Manabu; Toda, Hiroshi; Ono, Takashi; Konno, Hayato; Motoyama, Satoru; Ogawa, Jun–ichi

doi:10.1007/s13277-010-0113-x

Cited by 8 publications

(9 citation statements)

References 18 publications

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“…In a mouse model of lung cancer (Lewis lung carcinoma), expression of CCR6 in tumor cells reduced metastatic potential (Sutherland et al, 2007). Similar to our findings, a study found that increased expression of CCR6 in tumor cells is an independent predictor of a better prognosis in patients with LUAD (Minamiya et al, 2011). A recent study showed that CCL20, in coordination with CCR6, can recruit Treg cells to tumor sites (Zhang et al, 2015).…”

Section: Discussionsupporting

confidence: 88%

Analysis of prognostic genes in the tumor microenvironment of lung adenocarcinoma

Zhao

Chen

et al. 2020

PeerJ

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Background Prognostic genes in the tumor microenvironment play an important role in immune biological processes and the response of cancer to immunotherapy. Thus, we aimed to assess new biomarkers that are associated with immune/stromal cells in lung adenocarcinomas (LUAD) using the ESTIMATE algorithm, which also significantly affects the prognosis of cancer. Methods The RNA sequencing (RNA-Seq) and clinical data of LUAD were downloaded from the the Cancer Genome Atlas (TCGA ). The immune and stromal scores were calculated for each sample using the ESTIMATE algorithm. The LUAD gene chip expression profile data and the clinical data (GSE37745, GSE11969, and GSE50081) were downloaded from the Gene Expression Omnibus (GEO) for subsequent validation analysis. Differentially expressed genes were calculated between high and low score groups. Univariate Cox regression analysis was performed on differentially expressed genes (DEGs) between the two groups to obtain initial prognosis genes. These were verified by three independent LUAD cohorts from the GEO database. Multivariate Cox regression was used to identify overall survival-related DEGs. UALCAN and the Human Protein Atlas were used to analyze the mRNA /protein expression levels of the target genes. Immune cell infiltration was evaluated using the Tumor Immune Estimation Resource (TIMER) and CIBERSORT methods, and stromal cell infiltration was assessed using xCell. Results In this study, immune scores and stromal scores are significantly associated with the clinical characteristics of LUAD, including T stage, M stage, pathological stage, and overall survival time. 530 DEGs (18 upregulated and 512 downregulated) were found to coexist in the difference analysis with the immune scores and stromal scores subgroup. Univariate Cox regression analysis showed that 286 of the 530 DEGs were survival-related genes (p < 0.05). Of the 286 genes initially identified, nine prognosis-related genes (CSF2RB, ITK, FLT3, CD79A, CCR4, CCR6, DOK2, AMPD1, and IGJ) were validated from three separate LUAD cohorts. In addition, functional analysis of DEGs also showed that various immunoregulatory molecular pathways, including regulation of immune response and the chemokine signaling pathways, were involved. Five genes (CCR6, ITK, CCR4, DOK2, and AMPD1) were identified as independent prognostic indicators of LUAD in specific data sets. The relationship between the expression levels of these genes and immune genes was assessed. We found that CCR6 mRNA and protein expression levels of LUAD were greater than in normal tissues. We evaluated the infiltration of immune cells and stromal cells in groups with high and low levels of expression of CCR6 in the TCGA LUAD cohort. In summary, we found a series of prognosis-related genes that were associated with the LUAD tumor microenvironment.

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Section: Discussionsupporting

confidence: 88%

Analysis of prognostic genes in the tumor microenvironment of lung adenocarcinoma

Zhao

Chen

et al. 2020

PeerJ

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“…The integrated analysis seen in Figure 4 revealed a potential role for several decitabine-derepressed genes (hypomethylated and upregulated) such as SLC14A2 and SLC 12A1 encoding transporters involved in drug uptake/efflux and attenuated isoosmolarity [41], CCR6 , which has been correlated with favorable prognosis in lung cancer patients [42], and UNC5CLII , an inhibitor of NF-kappaB activation that sensitized 293 cells to apoptosis [43]. In addition, methylation-dependent silencing of P4HA3 in B-cell lymphoma cell lines was previously shown to be reversible by DNMTI treatment [44], and PABPC5 has been associated with premature ovarian failure [45] but a role for either gene in OC has not been previously reported.…”

Section: Discussionmentioning

confidence: 99%

Decitabine reactivated pathways in platinum resistant ovarian cancer

et al. 2014

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Combination therapy with decitabine, a DNMTi and carboplatin resensitized chemoresistant ovarian cancer (OC) to platinum inducing promising clinical activity. We investigated gene-expression profiles in tumor biopsies to identify decitabine-reactivated pathways associated with clinical response. Gene-expression profiling was performed using RNA from paired tumor biopsies before and 8 days after decitabine from 17 patients with platinum resistant OC. Bioinformatic analysis included unsupervised hierarchical-clustering, pathway and GSEA distinguishing profiles of “responders” (progression-free survival, PFS>6months) and “non-responders” (PFS<6months). Functional validation of selected results was performed in OC cells/tumors. Pre-treatment tumors from responders expressed genes associated with enhanced glycosphingolipid biosynthesis, translational misregulation, decreased ABC transporter expression, TGF-β signaling, and numerous metabolic pathways. Analysis of post-treatment biopsies from responders revealed overexpression of genes associated with reduced Hedgehog pathway signaling, reduced DNA repair/replication, and cancer-associated metabolism. GO and GSEA analyses revealed upregulation of genes associated with glycosaminoglycan binding, cell-matrix adhesion, and cell-substrate adhesion. Computational findings were substantiated by experimental validation of expression of key genes involved in two critical pathways affected by decitabine (TGF-β and Hh). Gene-expression profiling identified specific pathways altered by decitabine and associated with platinum-resensitization and clinical benefit in OC. Our data could influence patient stratification for future studies using epigenetic therapies.

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“…These results suggest that a heat-stress-induced increase in membrane fluidity is one of the primary events, and it subsequently triggers a cascade of molecular events that eventually make T cells crosstalk more rapidly and efficiently with APCs. These cellular events, including the formation of TCR microclusters, consist of several adhesion and signaling molecules [44] , which accumulate at the immune synapse [45] . This is also known as the central supramolecular activation complex [46] .…”

Section: Hyperthermia Enhances Immune Systems In Response To Cancermentioning

confidence: 99%

Cancer immunity and therapy using hyperthermia with immunotherapy, radiotherapy, chemotherapy, and surgery

Yagawa¹,

Tanigawa²,

Kobayashi³

et al. 2017

JCMT

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Hyperthermia is a type of medical modality for cancer treatment using the biological effect of artificially induced heat. Even though the intrinsic effects of elevated body temperature in cancer tissues are poorly understood, increasing the temperature of the body has been recognized as a popular therapeutic method for tumorous lesions as well as infectious diseases since ancient times. Recently accumulated evidence has shown that hyperthermia amplifies immune responses in the body against cancer while decreasing the immune suppression and immune escape of cancer. It also shows that hyperthermia inhibits the repair of damaged cancer cells after chemotherapy or radiotherapy. These perceptions indicate that hyperthermia has potential for cancer therapy in conjunction with immunotherapy, chemotherapy, radiotherapy, and surgery. Paradoxically, the anticancer effect of hyperthermia alone has not yet been adequately exploited because deep heating techniques and devices to aggregate heat effects only in cancer tissues are difficult in practical terms. This review article focuses on the current understanding concerning cancer immunity and involvement of hyperthermia and the innate and adoptive immune system. The potential for combination therapy with hyperthermia and chemotherapy, radiotherapy, and surgery is also discussed. Key words:Hyperthermia, cancer immunity, chemosensitizer, radiosensitizer, combination cancer therapy, hyperthermic intraoperative peritoneal chemotherapy ABSTRACTArticle history:

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Expression of the chemokine receptor CCR6 correlates with a favorable prognosis in patients with adenocarcinoma of the lung

Cited by 8 publications

References 18 publications

Analysis of prognostic genes in the tumor microenvironment of lung adenocarcinoma

Analysis of prognostic genes in the tumor microenvironment of lung adenocarcinoma

Decitabine reactivated pathways in platinum resistant ovarian cancer

Cancer immunity and therapy using hyperthermia with immunotherapy, radiotherapy, chemotherapy, and surgery

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