GRIK2 is a target for bladder cancer stem-like cell-targeting immunotherapy

Miyata, Haruka; Hirohashi, Yoshihiko; Yamada, Shuhei; Yanagawa, Junko; Murai, Aiko; Hashimoto, Shinichi; Tokita, Serina; Hori, Kanta; Abe, Takashige; Kubo, Terufumi; Tsukahara, Tomohide; Kanaseki, Takayuki; Shinohara, Nobuo; Torigoe, Toshihiko

doi:10.1007/s00262-021-03025-z

Cited by 9 publications

(13 citation statements)

References 41 publications

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“…Thus, treatment resistance and CSCs might be an overlapping population in heterogenous cancer cells. Indeed, we found that CLSPN is overexpressed in UM-UC-3 CR cells, and our previous study revealed that CLSPN peptide is expressed in UM-UC-3 H10 cells, a CSC-like clone derived from UM-UC-3 cells [12]. CSCs are resistant to treatment by the expression of anti-apoptosis proteins or transporters [25].…”

Section: Discussionmentioning

confidence: 61%

“…The number of CSCs/CICs was estimated using the Extreme Limiting Dilution Analysis (ELDA) website (http://bioinf.wehi.edu.au/software/elda/) [11]. Resistance to CDDP was assessed as previously described [12], using a WST-8 assay (Dojindo Molecular Technologies, Kumamoto, Japan).…”

Section: Establishment Of a Um-uc3 Cddp-resistant (Cr) Cell Linementioning

confidence: 99%

“…CAGE library preparation, sequencing, mapping, gene expression, motif discovery analysis, and Gene Ontology enrichment analysis were performed by DNAFORM (Yokohama, Japan) as previously described [12]. CAGE tag count data were clustered by CAGEr [14] using the Paraclu algorithm [15] with default parameters.…”

Section: Cap Analysis Of Gene Expression (Cage) Analysismentioning

confidence: 99%

“…For CTL culture, interleukin (IL)-2 and IL-15 (PeproTech, Cranbury, NJ) were used at nal concentrations of 10 U/mL and 10 ng/mL respectively. An IFNγ ELISPOT assay was performed as previously described [12].…”

Section: Cytotoxic T Lymphocyte (Ctl) Induction Elispot Assay and Est...mentioning

confidence: 99%

“…To narrow down the candidate genes, we referenced HLA ligandome analysis and a public database of gene expression (GTExPortal: https://www.gtexportal.org). Previously, we performed HLA ligandome analysis using UM-UC-3 cells to identify HLA-A2-bound antigenic peptides [12]. Thus, we screened genes that were upregulated in CR cells, that encoded HLA-A2-bound antigenic peptides identi ed by HLA ligandome analysis, and whose expression in normal organs was less than 2 transcripts per million.…”

Section: Clspn Expression Is Upregulated In Cr Cellsmentioning

confidence: 99%

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Cisplatin resistance driver claspin is a target for immunotherapy in urothelial carcinoma

Yamada

Miyata

Isono

et al. 2023

Cancer Immunol Immunother

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Bladder cancer is a major and fatal urological disease. Cisplatin is a key drug for the treatment of bladder cancer, especially in muscle-invasive cases. In most cases of bladder cancer, cisplatin is effective; however, resistance to cisplatin has a signi cant negative impact on prognosis. Thus, a treatment strategy for cisplatin-resistant bladder cancer is essential to improve the prognosis. In this study, we established a cisplatin-resistant (CR) bladder cancer cell line using a urothelial carcinoma cell line (UM-UC-3 cells). We screened for potential targets in CR cells and found that claspin (CLSPN) was overexpressed. CLSPNmRNA knockdown revealed that CLSPN had a role in cisplatin resistance in CR cells. In our previous study, we identi ed human leukocyte antigen (HLA)-A*02:01-restricted CLSPN peptide by HLA ligandome analysis. Thus, we generated a CLSPN peptide-speci c cytotoxic T lymphocyte (CTL) clone that recognized CR cells at a higher level than wild-type UM-UC-3 cells. These ndings indicate that CLSPN is a driver of cisplatin resistance and CLSPN peptide-speci c immunotherapy may be effective for cisplatin-resistant cases.

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Section: Discussionmentioning

confidence: 61%

Section: Establishment Of a Um-uc3 Cddp-resistant (Cr) Cell Linementioning

confidence: 99%

Section: Cap Analysis Of Gene Expression (Cage) Analysismentioning

confidence: 99%

Section: Cytotoxic T Lymphocyte (Ctl) Induction Elispot Assay and Est...mentioning

confidence: 99%

Section: Clspn Expression Is Upregulated In Cr Cellsmentioning

confidence: 99%

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Cisplatin resistance driver claspin is a target for immunotherapy in urothelial carcinoma

Yamada

Miyata

Isono

et al. 2023

Cancer Immunol Immunother

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Fusion with type 2 macrophages induces melanoma cell heterogeneity that potentiates immunological escape from cytotoxic T lymphocytes

Minowa

Hirohashi

Murata

et al. 2023

The Journal of Pathology

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Evasion from immunity is a major obstacle to the achievement of successful cancer immunotherapy. Hybrids derived from cell–cell fusion are theoretically associated with tumor heterogeneity and progression by conferring novel properties on tumor cells, including drug resistance and metastatic capacity; however, their impact on immune evasion remains unknown. Here, we investigated the potency of tumor–macrophage hybrids in immune evasion. Hybrids were established by co‐culture of a melanoma cell line (A375 cells) and type 2 macrophages. The hybrids showed greater migration ability and greater tumorigenicity than the parental melanoma cells. The hybrids showed heterogeneous sensitivity to New York esophageal squamous cell carcinoma‐1 (NY‐ESO‐1)‐specific T‐cell receptor‐transduced T (TCR‐T) cells and two out of four hybrid clones showed less sensitivity to TCR‐T compared with the parental cells. An in vitro tumor heterogeneity model revealed that the TCR‐T cells preferentially killed the parental cells compared with the hybrids and the survival rate of the hybrids was higher than that of the parental cells, indicating that the hybrids evade killing by TCR‐T cells efficiently. Analysis of a single‐cell RNA sequencing dataset of patients with melanoma revealed that a few macrophages expressed RNA encoding melanoma differentiation antigens including melan A, tyrosinase, and premelanosome protein, which indicated the presence of hybrids in primary melanoma. In addition, the number of potential hybrids was correlated with a poorer response to immune checkpoint blockade. These results provide evidence that melanoma–macrophage fusion has a role in tumor heterogeneity and immune evasion. © 2023 The Pathological Society of Great Britain and Ireland.

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Cancer Immunotherapies Targeting Cancer Stem Cells: Concepts, Applications, and Advances

Farhangnia,

Shokri,

Akbarpour

et al. 2024

Interdisciplinary Cancer Research

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GRIK2 is a target for bladder cancer stem-like cell-targeting immunotherapy

Cited by 9 publications

References 41 publications

Cisplatin resistance driver claspin is a target for immunotherapy in urothelial carcinoma

Cisplatin resistance driver claspin is a target for immunotherapy in urothelial carcinoma

Fusion with type 2 macrophages induces melanoma cell heterogeneity that potentiates immunological escape from cytotoxic T lymphocytes

Cancer Immunotherapies Targeting Cancer Stem Cells: Concepts, Applications, and Advances

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