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A new strategy using ALDHhigh-CD8+T cells to inhibit tumorigenesis.

Luo H, Zeng C, Fang C, Seeruttun SR, Lv L, Wang W - PLoS ONE (2014)

Bottom Line: Further study demonstrated that ALDHhigh-CD8+T cells conferred more significant antitumor effects, resulting in the inhibition of tumor growth and prolonged survival.And the ALDHhigh-CD8+T cells-mediated anti-tumor immunity might be due to the directly targeting against ALDHhigh cancer stem cells (CSCs).This study shows that ALDHhigh-CD8+T cells mediate anti-tumor immunity by selectively targeting cancer stem cells, which result in inhibiting tumor growth and prolonging the survival of tumor-bearing mice, which provides a new strategy using ALDHhigh-CD8+T cells to treat tumors.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, the Third People's Hospital of Chongqing, Chongqing, P. R. China; State Key Laboratory of Oncology in South China, Guangzhou, P. R. China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China.

ABSTRACT

Background: Currently, many studies suggest that cancer stem cells (CSCs) are responsible for tumor initiation, tumorigenesis, metastasis and recurrence. CSCs have been identified from various human and murine tumors. The identification of CSCs allows us to develop strategies to target the CSCs.

Methods and results: In this study, we used ALDEFLUOR as a single marker to isolate the CSCs from the human lung cancer cell line H460. We then characterized the CSCs by testing their sphere formation ability and tumorigenicity. Furthermore, we used CSC lysate-pulsed dendritic cells to stimulate CD8+T cells as a treatment strategy. Our study demonstrated that ALDEFLUOR could be used as a single marker to identify CSCs from the human lung cancer cell line H460. The ALDHhigh cells could form more spheres and were more tumorigenic than the ALDHlow cells. Further study demonstrated that ALDHhigh-CD8+T cells conferred more significant antitumor effects, resulting in the inhibition of tumor growth and prolonged survival. And the ALDHhigh-CD8+T cells-mediated anti-tumor immunity might be due to the directly targeting against ALDHhigh cancer stem cells (CSCs).

Conclusions: This study shows that ALDHhigh-CD8+T cells mediate anti-tumor immunity by selectively targeting cancer stem cells, which result in inhibiting tumor growth and prolonging the survival of tumor-bearing mice, which provides a new strategy using ALDHhigh-CD8+T cells to treat tumors.

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Cytotoxicities of effect T cells against cancer stem cells and tumor cells.The killing was measured by an LDH release assay as described in the Materials and Methods. Higher % of cytotoxicity means more cell lysis. (A) Cytotoxicities of CSCs mediated by the H-T, ALDHlow-T and ALDHhigh-T are shown. (B) Cytotoxicities of unsorted H460 cells mediated by the H-T, ALDHlow-T and ALDHhigh-T are shown. (C) ALDHhigh-T could kill much more CSCs than unsorted tumor cells.
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pone-0103193-g006: Cytotoxicities of effect T cells against cancer stem cells and tumor cells.The killing was measured by an LDH release assay as described in the Materials and Methods. Higher % of cytotoxicity means more cell lysis. (A) Cytotoxicities of CSCs mediated by the H-T, ALDHlow-T and ALDHhigh-T are shown. (B) Cytotoxicities of unsorted H460 cells mediated by the H-T, ALDHlow-T and ALDHhigh-T are shown. (C) ALDHhigh-T could kill much more CSCs than unsorted tumor cells.

Mentions: To study the underlying mechanism of the anti-tumor immunity of the ALDHhigh-CD8+ T cells, we studied the cytotoxicities of the effect T cells in vitro. These activated effect T cells were assessed for cytotoxicity against ALDHhigh H460 cells or unsorted H460 tumor cells. ALDHhigh-CD8+ T killed H460 CSCs efficiently and significantly more than H- CD8+ T (Figure 6A, Pā€Š=ā€Š0.0011) and ALDHlow- CD8+ T (Figure 6A, P<0.0001). Concurrently, the killing of unsorted H460 cells by ALDHhigh-CD8+ T was significantly less effective compared with both H- CD8+ T and ALDHlow- CD8+ T (Figure 6B, P<0.0001). As shown in Figure 6C, the ALDHhigh-CD8+ T could kill much more ALDHhigh H460 cells than unsorted H460 tumor cells (P<0.0001). These date suggested that the enhanced ALDHhigh-CD8+ T-induced anti-tumor immunity might be due to directly and selectively targeting of CSCs.


A new strategy using ALDHhigh-CD8+T cells to inhibit tumorigenesis.

Luo H, Zeng C, Fang C, Seeruttun SR, Lv L, Wang W - PLoS ONE (2014)

Cytotoxicities of effect T cells against cancer stem cells and tumor cells.The killing was measured by an LDH release assay as described in the Materials and Methods. Higher % of cytotoxicity means more cell lysis. (A) Cytotoxicities of CSCs mediated by the H-T, ALDHlow-T and ALDHhigh-T are shown. (B) Cytotoxicities of unsorted H460 cells mediated by the H-T, ALDHlow-T and ALDHhigh-T are shown. (C) ALDHhigh-T could kill much more CSCs than unsorted tumor cells.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4126683&req=5

pone-0103193-g006: Cytotoxicities of effect T cells against cancer stem cells and tumor cells.The killing was measured by an LDH release assay as described in the Materials and Methods. Higher % of cytotoxicity means more cell lysis. (A) Cytotoxicities of CSCs mediated by the H-T, ALDHlow-T and ALDHhigh-T are shown. (B) Cytotoxicities of unsorted H460 cells mediated by the H-T, ALDHlow-T and ALDHhigh-T are shown. (C) ALDHhigh-T could kill much more CSCs than unsorted tumor cells.
Mentions: To study the underlying mechanism of the anti-tumor immunity of the ALDHhigh-CD8+ T cells, we studied the cytotoxicities of the effect T cells in vitro. These activated effect T cells were assessed for cytotoxicity against ALDHhigh H460 cells or unsorted H460 tumor cells. ALDHhigh-CD8+ T killed H460 CSCs efficiently and significantly more than H- CD8+ T (Figure 6A, Pā€Š=ā€Š0.0011) and ALDHlow- CD8+ T (Figure 6A, P<0.0001). Concurrently, the killing of unsorted H460 cells by ALDHhigh-CD8+ T was significantly less effective compared with both H- CD8+ T and ALDHlow- CD8+ T (Figure 6B, P<0.0001). As shown in Figure 6C, the ALDHhigh-CD8+ T could kill much more ALDHhigh H460 cells than unsorted H460 tumor cells (P<0.0001). These date suggested that the enhanced ALDHhigh-CD8+ T-induced anti-tumor immunity might be due to directly and selectively targeting of CSCs.

Bottom Line: Further study demonstrated that ALDHhigh-CD8+T cells conferred more significant antitumor effects, resulting in the inhibition of tumor growth and prolonged survival.And the ALDHhigh-CD8+T cells-mediated anti-tumor immunity might be due to the directly targeting against ALDHhigh cancer stem cells (CSCs).This study shows that ALDHhigh-CD8+T cells mediate anti-tumor immunity by selectively targeting cancer stem cells, which result in inhibiting tumor growth and prolonging the survival of tumor-bearing mice, which provides a new strategy using ALDHhigh-CD8+T cells to treat tumors.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, the Third People's Hospital of Chongqing, Chongqing, P. R. China; State Key Laboratory of Oncology in South China, Guangzhou, P. R. China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China.

ABSTRACT

Background: Currently, many studies suggest that cancer stem cells (CSCs) are responsible for tumor initiation, tumorigenesis, metastasis and recurrence. CSCs have been identified from various human and murine tumors. The identification of CSCs allows us to develop strategies to target the CSCs.

Methods and results: In this study, we used ALDEFLUOR as a single marker to isolate the CSCs from the human lung cancer cell line H460. We then characterized the CSCs by testing their sphere formation ability and tumorigenicity. Furthermore, we used CSC lysate-pulsed dendritic cells to stimulate CD8+T cells as a treatment strategy. Our study demonstrated that ALDEFLUOR could be used as a single marker to identify CSCs from the human lung cancer cell line H460. The ALDHhigh cells could form more spheres and were more tumorigenic than the ALDHlow cells. Further study demonstrated that ALDHhigh-CD8+T cells conferred more significant antitumor effects, resulting in the inhibition of tumor growth and prolonged survival. And the ALDHhigh-CD8+T cells-mediated anti-tumor immunity might be due to the directly targeting against ALDHhigh cancer stem cells (CSCs).

Conclusions: This study shows that ALDHhigh-CD8+T cells mediate anti-tumor immunity by selectively targeting cancer stem cells, which result in inhibiting tumor growth and prolonging the survival of tumor-bearing mice, which provides a new strategy using ALDHhigh-CD8+T cells to treat tumors.

Show MeSH
Related in: MedlinePlus