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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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Related in: MedlinePlus

Tumorigenicity of the ALDHhigh and ALDHlow H460 cells.An equal number of ALDHhigh and ALDHlow cells were inoculated into the opposite flanks of the same individuals. The sizes of the tumors were measured 3 times per week. (A) The tumor sizes of mice subjected to ALDHhigh H460 cells were much more larger than the ALDHlow H460 cells. (B–C) show the representative tumor growth curves from 3 different mice.
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pone-0103193-g003: Tumorigenicity of the ALDHhigh and ALDHlow H460 cells.An equal number of ALDHhigh and ALDHlow cells were inoculated into the opposite flanks of the same individuals. The sizes of the tumors were measured 3 times per week. (A) The tumor sizes of mice subjected to ALDHhigh H460 cells were much more larger than the ALDHlow H460 cells. (B–C) show the representative tumor growth curves from 3 different mice.

Mentions: It has been reported that cancer stem cells are more capable of forming tumors than unsorted tumor cells. A very small number of CSCs can form tumors. To test this hypothesis, an equal number of ALDHhigh cells and ALDHlow cells were subcutaneously injected into the opposite flanks of nude mice. After the tumor cells were injected, both the ALDHhigh and ALDHlow cells developed into a tumor mass. However, the volumes of the tumors generated from the ALDHhigh cells were much larger than the tumors generated from the ALDHlow cells (Figure 3A, P = 0.0003)). Figure 3B–D show the representative growth curves of the tumors from 3 different mice. These data suggest that the ALDHhighH460 tumor cells were much more tumorigenic than the ALDHlow cells.


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)

Tumorigenicity of the ALDHhigh and ALDHlow H460 cells.An equal number of ALDHhigh and ALDHlow cells were inoculated into the opposite flanks of the same individuals. The sizes of the tumors were measured 3 times per week. (A) The tumor sizes of mice subjected to ALDHhigh H460 cells were much more larger than the ALDHlow H460 cells. (B–C) show the representative tumor growth curves from 3 different mice.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0103193-g003: Tumorigenicity of the ALDHhigh and ALDHlow H460 cells.An equal number of ALDHhigh and ALDHlow cells were inoculated into the opposite flanks of the same individuals. The sizes of the tumors were measured 3 times per week. (A) The tumor sizes of mice subjected to ALDHhigh H460 cells were much more larger than the ALDHlow H460 cells. (B–C) show the representative tumor growth curves from 3 different mice.
Mentions: It has been reported that cancer stem cells are more capable of forming tumors than unsorted tumor cells. A very small number of CSCs can form tumors. To test this hypothesis, an equal number of ALDHhigh cells and ALDHlow cells were subcutaneously injected into the opposite flanks of nude mice. After the tumor cells were injected, both the ALDHhigh and ALDHlow cells developed into a tumor mass. However, the volumes of the tumors generated from the ALDHhigh cells were much larger than the tumors generated from the ALDHlow cells (Figure 3A, P = 0.0003)). Figure 3B–D show the representative growth curves of the tumors from 3 different mice. These data suggest that the ALDHhighH460 tumor cells were much more tumorigenic than the ALDHlow cells.

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