Immune responses to human cancer stem‐like cells/cancer‐initiating cells

Hirohashi, Yoshihiko; Torigoe, Toshihiko; Tsukahara, Tomohide; Kanaseki, Takayuki; Kochin, Vitaly; Sato, Noriyuki

doi:10.1111/cas.12830

Cited by 72 publications

(67 citation statements)

References 58 publications

(74 reference statements)

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“…Low expression levels of melanoma antigens in melanoma-initiating cells are thought to be the reason for resistance to peptide vaccination therapies using melanoma antigens (12). And recent studies indicate that CICs may contribute to make immunosuppressive microenvironment (13). We therefore hypothesized that CIC-targeting immunotherapy might improve the efficiency of cancer immunotherapy.…”

Section: Introductionmentioning

confidence: 99%

Olfactory Receptor Family 7 Subfamily C Member 1 Is a Novel Marker of Colon Cancer–Initiating Cells and Is a Potent Target of Immunotherapy

Morita

Hirohashi

Torigoe

et al. 2016

Clinical Cancer Research

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Purpose: Cancer-initiating cells (CICs) are thought to be essential for tumor maintenance, recurrence, and distant metastasis, and they are therefore reasonable targets for cancer therapy. Cancer immunotherapy is a novel approach to target cancer. In this study, we aimed to establish novel CIC-targeting immunotherapy.Experimental Design: Colorectal cancer (CRC) CICs were isolated as side population (SP) cells. The gene expression profile of CRC CICs was analyzed by cDNA microarray and RT-PCR. Protein expression of olfactory receptor family 7 subfamily C member 1 (OR7C1) were analyzed by Western blot and immunohistochemical staining. The functions of OR7C1 were analyzed by gene overexpression and gene knockdown using siRNAs. OR7C1-positive cells were isolated by a flow cytometer and analyzed. CTLs specific for OR7C1 peptide were generated, and the antitumor effect was addressed by mice adoptive transfer model.Results: OR7C1 has essential roles in the maintenance of colon CICs, and the OR7C1-positive population showed higher tumorigenicity than that of the OR7C1-negative population, indicating that OR7C1 is a novel functional marker for colon CIC. Immunohistochemical staining revealed that OR7C1 high expression was correlated with poorer prognosis in CRC patients. OR7C1-derived antigenic peptide-specific CTLs showed specific cytotoxicity for CICs, and an OR7C1-specific CTL clone showed a greater antitumor effect than did a CTL clone targeting all cancer cells in a CTL adoptive transfer mouse model.Conclusions: OR7C1 is a novel marker for colon CICs and can be a target of potent CIC-targeting immunotherapy. Clin Cancer Res; 22(13); 3298-309. Ó2016 AACR.

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Section: Introductionmentioning

confidence: 99%

Olfactory Receptor Family 7 Subfamily C Member 1 Is a Novel Marker of Colon Cancer–Initiating Cells and Is a Potent Target of Immunotherapy

Morita

Hirohashi

Torigoe

et al. 2016

Clinical Cancer Research

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“…Dai et al (19) reported that CTLA-4 was over expressed in allogeneic mesenchymal stem cells and promoted osteogenic differentiation. Shinoyama et al (25) revealed that CTLA-4 promoted neuronal differentiation in the grafts of embryonic stem cell-derived Studies have demonstrated that MSCs drive the initiation and progression of a melanoma based on the capacity for self-renewal, multiple differentiation, chemoresistance and immune evasion (2,3). Thus, targeting the survival mechanisms utilized by MSCs may be the most effective way to cure melanoma.…”

Section: Discussionmentioning

confidence: 99%

“…It has been hypothesized that melanoma stem cells (MSCs) possess the capacity for self-renewal, differentiation, chemoresistance and immune evasion (2,3). Thus, understanding the mechanism underlying melanoma progression may contribute to the targeted killing of MSCs, which may improve the efficacy of anticancer therapies and decrease the risk of relapse and progression.…”

Section: Introductionmentioning

confidence: 99%

Potential function of CTLA‑4 in the tumourigenic capacity of melanoma stem cells

Zhang

Dang

et al. 2018

Oncol Lett

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Abstract. Extensive clinical evidence supports that cytotoxic T lymphocyte antigen-4 (CTLA-4) is expressed in a variety of human malignant tumour cells in addition to T cells. In certain types of cancer, the overexpression of CTLA-4 is associated with poor patient prognosis. However, few studies have demonstrated the effects of tumour-intrinsic CTLA-4 in cancer stem cells, including melanoma stem cells (MSCs). In the present study, it was demonstrated that melanoma cell-intrinsic CTLA-4 induced tumour cell proliferation in vitro and suppressed tumour cell apoptosis. Furthermore, CTLA-4 was expressed in aldehyde dehydrogenase (ALDH) + MSCs. CTLA-4 inhibited MSCs proliferation in vitro by blocking antibodies and significantly downregulated ALDH1A1, ALDH1A3 and ALDH2 mRNA expression (P<0.01). Functionally, blocking CTLA-4 in melanoma cell lines suppressed the properties of stem-like cells, including ALDH activity and significantly suppressed the ability of these cells to form spheres in vitro (P<0.05). In addition, the blocking of CTLA-4 in melanoma cells suppressed the properties of stem-like cells in vivo, including the capacity for tumourigenesis. The presence of residual ALDH + MSCs within the tumour was observed, and the blocking CTLA-4 significantly decreased the number of residual ALDH + MSCs in vivo (P<0.01). Altogether, these results indicate the identification of a novel mechanism underlying melanoma progression in the present study and that CTLA-4-targeted therapy may benefit candidate CTLA-4-targeted therapy by improving the long-term outcome for patients with advanced stages of melanoma.

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“…Importantly, chemoresistant CSCs preferentially express stem cell markers, including OCT3/4, ABCG2, nestin, SOX2, Bmi-1, Notch-1, CD44, CD133 and CD177 [56]. CSCs also overexpress a range of known tumour-associated antigens, such as survivin, MUC1, hTERT, HER2, CERP55, COA-1 and WT1 [58]. In addition, MUC1 expression is upregulated in chemoresistant CSCs which are efficiently lysed by MUC1-specific CTLs in mice [59].…”

Section: Fusion Of Dcs and Cancer Stem Cellsmentioning

confidence: 99%