Hiding in the dark: pan-cancer characterization of expression and clinical relevance of CD40 to immune checkpoint blockade therapy

Yan, Chi; Richmond, Ann

doi:10.1186/s12943-021-01442-3

Cited by 32 publications

(26 citation statements)

References 19 publications

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“…First, the ESTIMATE algorithm was conducted to estimate tumor purity, ESTIMATE score, immune score, and stromal score [ 16 ], and their correlations with CDCP1 expression were next assessed. Next, several gene markers related to the tumor microenvironment (TME) as well as immune checkpoints were obtained from a previous publication [ 17 ] and their correlations with CDCP1 expression were evaluated. Furthermore, the correlations between CDCP1 expression and 150 immune-related genes, including chemokines, receptors, MHC molecules, immunoinhibitors, and immunostimulators, were assessed.…”

Section: Methodsmentioning

confidence: 99%

Overexpression of CDCP1 is Associated with Poor Prognosis and Enhanced Immune Checkpoints Expressions in Breast Cancer

Zhao

Mei

Wang

et al. 2022

Journal of Oncology

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CUB-domain containing protein 1 (CDCP1) is a transmembrane protein acting as an effector of SRC family kinases, which play an oncogenic role in multiple human cancers. However, its clinical and immune correlations in breast cancer (BrCa) have not been explored. To define the expression, prognostic value, and potential molecular role of CDCP1 in BrCa, multiple public datasets, and an in-house cohort were used. Compared with paratumor tissue, CDCP1 was remarkably upregulated in the tumor tissues at both mRNA and protein levels. In the in-house cohort, CDCP1 protein expression was related to several clinicopathological parameters, including age, ER status, PR status, molecular type, and survival status. Kaplan–Meier analysis and Cox regression analysis exhibited that CDCP1 was an important prognostic biomarker in BrCa. In addition, enrichment analysis uncovered that CDCP1 was not only involved in multiple oncogenic pathways, but correlated with overexpression of immune checkpoints. Overall, we reported that increased expression of CDCP1 is a favorable prognostic factor in patients with BrCa. In addition, the correlations between CDCP1 and immune checkpoints provide a novel insight into the adjuvant treatment for immune checkpoint blockade via targeting CDCP1.

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Section: Methodsmentioning

confidence: 99%

Overexpression of CDCP1 is Associated with Poor Prognosis and Enhanced Immune Checkpoints Expressions in Breast Cancer

Zhao

Mei

Wang

et al. 2022

Journal of Oncology

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“…The work identified that cluster of differentiation 27 and 40 (CD27, CD40), and herpes virus entry mediator (HVEM) gene expression is correlated to a better response to immune checkpoint blockade. CD27 and CD40 play a key role in activating T cells and anti-tumor immune responses [ 86 – 88 ], while HVEM is involved in both activating and inhibiting it [ 89 ]. The study also showed the expression of other genes such as the cluster of differentiation 200 and 276 (CD200, CD276/B7-H3), T-cell immunoglobulin domain and mucin domain 3 (TIM-3), and v-domain immunoglobulin suppressor of T cell activation (VISTA) correlated with a worse response [ 85 ].…”

Section: Datasets With Anti-pd-1 and Anti-ctla-4 Combination Therapymentioning

confidence: 99%

Transcriptomic datasets of cancer patients treated with immune-checkpoint inhibitors: a systematic review

Kovács

Győrffy

2022

J Transl Med

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The availability of immune-checkpoint inhibitors (ICI) in the last decade has resulted in a paradigm shift in certain areas of oncology. Patients can be treated either by a monotherapy of anti-CTLA-4 (tremelimumab or ipilimumab), anti-PD-1 (nivolumab or pembrolizumab), or anti-PD-L1 (avelumab or atezolizumab or durvalumab) or as combination therapy of anti-CTLA-4 and anti-PD-1. To maximize the clinical treatment benefit of cancer immunotherapy, the prediction of the actual immune response by the identification and application of clinically useful biomarkers will be required. Whole transcriptomic datasets of patients with ICI treatment could provide the basis for large-scale discovery and ranking of such potential biomarker candidates. In this review, we summarize currently available transcriptomic data from different biological sources (whole blood, fresh-frozen tissue, FFPE) obtained by different methods (microarray, RNA-Seq, RT-qPCR). We directly include only results from clinical trials and other investigations where an ICI treatment was administered. The available datasets are grouped based on the administered treatment and we also summarize the most important results in the individual cohorts. We discuss the limitations and shortcomings of the available datasets. Finally, a subset of animal studies is reviewed to provide an overview of potential in vivo ICI investigations. Our review can provide a swift reference for researchers aiming to find the most suitable study for their investigation, thus saving a significant amount of time.

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“…Additionally, the potential value of various new inhibitory immune checkpoints (BTLA [ 130 – 132 ], B7 family [ 133 – 137 ], IDO-1 [ 138 , 139 ], LAG-3 [ 140 , 141 ]) and costimulatory molecules (GITR [ 142 – 145 ], ICOS [ 146 – 148 ], OX40 [ 149 – 151 ], 4-1BB [ 152 – 154 ], CD40 [ 155 , 156 ], CD27 [ 157 – 159 ]) has been confirmed for melanoma treatments. The efficacy and safety of some inhibitory checkpoints and costimulatory molecules in melanoma treatments, alone or combined with ICIs, have been preliminarily elucidated in early clinical trials [ 160 – 173 ] and others are in progress (NCT04773951, NCT04137900, NCT02554812).…”

Section: Future Directionsmentioning

confidence: 99%

Advanced Acral Melanoma Therapies: Current Status and Future Directions

Zhang

Lan

2022

Curr. Treat. Options in Oncol.

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Opinion statementMelanoma is one of the deadliest malignancies. Its incidence has been significantly increasing in most countries in recent decades. Acral melanoma (AM), a peculiar subgroup of melanoma occurring on the palms, soles, and nails, is the main subtype of melanoma in people of color and is extremely rare in Caucasians. Although great progress has been made in melanoma treatment in recent years, patients with AM have shown limited benefit from current therapies and thus consequently have worse overall survival rates. Achieving durable therapeutic responses in this high-risk melanoma subtype represents one of the greatest challenges in the field. The frequency of BRAF mutations in AM is much lower than that in cutaneous melanoma, which prevents most AM patients from receiving treatment with BRAF inhibitors. However, AM has more frequent mutations such as KIT and CDK4/6, so targeted therapy may still improve the survival of some AM patients in the future. AM may be less susceptible to immune checkpoint inhibitors because of the poor immunogenicity. Therefore, how to enhance the immune response to the tumor cells may be the key to the application of immune checkpoint inhibitors in advanced AM. Anti-angiogenic drugs, albumin paclitaxel, or interferons are thought to enhance the effectiveness of immune checkpoint inhibitors. Combination therapies based on the backbone of PD-1 are more likely to provide greater clinical benefits. Understanding the molecular landscapes and immune microenvironment of AM will help optimize our combinatory strategies.

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Hiding in the dark: pan-cancer characterization of expression and clinical relevance of CD40 to immune checkpoint blockade therapy

Cited by 32 publications

References 19 publications

Overexpression of CDCP1 is Associated with Poor Prognosis and Enhanced Immune Checkpoints Expressions in Breast Cancer

Overexpression of CDCP1 is Associated with Poor Prognosis and Enhanced Immune Checkpoints Expressions in Breast Cancer

Transcriptomic datasets of cancer patients treated with immune-checkpoint inhibitors: a systematic review

Advanced Acral Melanoma Therapies: Current Status and Future Directions

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