Development of multiple cutaneous immune-related adverse events among cancer patients after immune checkpoint blockade

Asdourian, Maria S.; Shah, Nishi; Jacoby, Ted V.; Semenov, Yevgeniy R.; Otto, Tim; Thompson, Leah L.; Dee, Edward Christopher; Reynolds, Kerry L.; Chen, Steven T

doi:10.1016/j.jaad.2022.06.030

Cited by 4 publications

(3 citation statements)

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“…The main strategy of immunotherapy is to block immune checkpoints ( 42 ). Therefore, it is essential to increase the response of tumor cells to immune checkpoint inhibitors and cytokines ( 43 , 44 ). Given that the upregulation of TPR was significantly correlated with immune regulators and chemokines, it is proposed that targeting TPR may improve immunotherapy effectiveness.…”

Section: Discussionmentioning

confidence: 99%

TPR is a prognostic biomarker and potential therapeutic target associated with immune infiltration in hepatocellular carcinoma

Long,

Wu,

Wang

et al. 2024

Mol Clin Oncol

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Liver cancer is the fourth leading cause of cancer-related mortality worldwide and hepatocellular carcinoma (HCC) is the most common primary liver cancer. In the present study, it was demonstrated that translocated promoter region (TPR) was upregulated in tumor tissues and associated with prognosis and immune infiltration in HCC. The clinical outcome of patients with HCC with aberrant expression of TPR was examined using multiple databases, including Gene Expression Omnibus, The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression, Kaplan-Meier (KM) Plotter and Xiantao tool. The clinicopathologic characteristics of patients from TCGA database that were associated with overall survival were assessed using Cox regression and KM analysis. The potential hallmarks associated with TPR expression were further predicted by Metascape and Gene Set Enrichment Analysis, and the relationship between TPR and immune infiltration was explored using the Tumor-Immune System Interactions Database and the Tumor Immune Estimation Resource. The results demonstrated that TPR expression was higher in HCC and its overexpression was associated with a worse prognosis, alongside a correlation with several clinical features. Furthermore, cell differentiation, a prospective new hallmark of cancer, was differentially enriched in the high TPR expression phenotype pathway. Moreover, TPR may also modulate the tumor immune microenvironment as it was significantly associated with immunoregulators and chemokines, as well as different tumor infiltration immune cells. According to the in vitro experiments, TPR silencing inhibited the phosphorylation of AKT and the proliferation of HCC cells. In summary, TPR may be a new marker and target for HCC therapy.

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Section: Discussionmentioning

confidence: 99%

TPR is a prognostic biomarker and potential therapeutic target associated with immune infiltration in hepatocellular carcinoma

Long,

Wu,

Wang

et al. 2024

Mol Clin Oncol

View full text Add to dashboard Cite

show abstract

“…Blocking immune checkpoints is the main strategy of immunotherapy ( 29 ). The most important thing is to enhance the response of tumor cells to immune checkpoint inhibitors and cytokines ( 30 , 31 ). According to TISIDB, TIMER and Xiantao tool, our results showed that the up-regulation of TIMM13 expression was not only related to PD1 and CTLA4, but also significantly related to cell response to chemokines.…”

Section: Discussionmentioning

confidence: 99%

TIMM13 as a prognostic biomarker and associated with immune infiltration in skin cutaneous melanoma (SKCM)

et al. 2022

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ObjectiveProviding protection against aggregation and guiding hydrophobic precursors through the mitochondria’s intermembrane space, this protein functions as a chaperone-like protein. SLC25A12 is imported by TIMM8 as a result of its interaction with TIMM13. In spite of this, it is still unknown how TIMM13 interacts with skin cutaneous melanoma (SKCM) and tumor-infiltrating lymphocytes (TILs).MethodsAberrant expression of TIMM13 in SKCM and its clinical outcome was evaluated with the help of multiple databases, including the Xiantao tool (https://www.xiantao.love/), HPA, and UALCAN. TISIDB and Tumor Immune Estimation Resources (TIMER) databases were applied to explore the association between TIMM13 and tumor infiltration immune cells. OS nomogram was constructed, and model performance was examined. Finally, TIMM13 protein expression was validated by immunohistochemistry (IHC).ResultsTIMM13 expression was higher in SKCM samples than in peritumor samples. TIMM13 was strongly associated with sample type, subgroup, cancer stage, lymph node stage, and worse survival. Further, upregulation of TIMM13 was significantly associated with immunoregulators, and chemokines, as well as T cells, B cells, monocytes, neutrophils, macrophages, and T-cell regulators. An analysis of bioinformatic data uncovered that TIMM13 expression was strongly associated with PD1 (T-cell exhaustion marker). The nomogram showed good predictive performance based on calibration plot. TIMM13 was highly expressed in melanoma tissue samples than in normal samples.ConclusionIn brief, TIMM13 may be a prognostic biomarker for SKCM. It might modulate the tumor immune microenvironment and lead to a poorer prognosis. In addition, it is necessary to study the targeted therapy of TIMM13.

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“…However, previous studies have been limited by cohort size, thus limiting generalizability. [6][7][8] In addition, the prior study approaches primarily utilized pairwise comparison analyses, which limited the examination of irAE relationships to two organ systems at a time. In this study, we leverage a population-level database and compare results to a multi-institutional cohort from a tertiary-level academic healthcare system to investigate the co-occurrence patterns irAEs and their impact on immunotherapy outcomes through non-negative matrix factorization (NMF), 9 which allows for multi-organ analyses.…”

mentioning

confidence: 99%

1241 Clusters of multi-organ toxicities are associated with improved survival among immune checkpoint inhibitor recipients: a population-level study

Chen,

Wan,

Roster

et al. 2023

Regular and Young Investigator Award Abstracts

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Figure 2 The results of NMF and hierarchical clustering on the consensus matrix. (A, B) The NMF results and clusters on the TriNetX cohort; C-D: The NMF results and clusters on the MGB cohort. The NMF decomposed the irAE count matrix into two low-rank matrices, representing the organ-level irAE factors (referred to as 'basis'; A, C) and the weights of irAE factors that comprise each patient (referred to as 'weight'; B and D), respectively. For the basis matrix, rows are organ systems, and columns are the irAE factors, each named by the dominant organ systems. For the weight matrix, columns are patients, rows are irAE factors, and the clustering results are presented at the top. Similar patterns were observed between the two basis matrices (A, C). Patients in both cohorts could be categorized into four groups (B, D) Cutaneous, Cutaneous +

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Development of multiple cutaneous immune-related adverse events among cancer patients after immune checkpoint blockade

Cited by 4 publications

References 5 publications

TPR is a prognostic biomarker and potential therapeutic target associated with immune infiltration in hepatocellular carcinoma

TPR is a prognostic biomarker and potential therapeutic target associated with immune infiltration in hepatocellular carcinoma

TIMM13 as a prognostic biomarker and associated with immune infiltration in skin cutaneous melanoma (SKCM)

1241 Clusters of multi-organ toxicities are associated with improved survival among immune checkpoint inhibitor recipients: a population-level study

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