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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

Sphere formation of the ALDHhigh and ALDHlow cells.A total of 10,000 isolated ALDHhigh or ALDHlow cells were cultured in serum-free medium. The representative photographs from the ALDHhigh cells (A) and ALDHlow cells (B) were taken on day 14. The ALDHhigh cells could form much more spheres than the ALDHlow H460 cells (C). The number of spheres were expressed as Mean± SEM, n = 4.
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pone-0103193-g002: Sphere formation of the ALDHhigh and ALDHlow cells.A total of 10,000 isolated ALDHhigh or ALDHlow cells were cultured in serum-free medium. The representative photographs from the ALDHhigh cells (A) and ALDHlow cells (B) were taken on day 14. The ALDHhigh cells could form much more spheres than the ALDHlow H460 cells (C). The number of spheres were expressed as Mean± SEM, n = 4.

Mentions: CSCs are characterized by their sphere formation ability, tumorigenesis and self-renewal. To verify whether the ALDEFLUOR-enriched population contained cancer stem cell-like cells, we first performed the sphere formation assay by culturing the ALDHhigh cells in serum-free medium; the ALDHlow cells were also cultured under these conditions and were used as a negative control. Compared to the ALDHlow cells, the ALDHhigh cells had an enhanced sphere forming ability. Figure 2A and B show representative pictures from the ALDHhigh and ALDHlow cells on day 14. We also counted the numbers of the spheres formed by ALDHhigh or ALDHlow H460 cells. As shown in Figure 2C, compared to ALDHlow H460 cells, the enriched ALDHhigh H460 cells could form much more spheres (Figure 2C, P = 0.0034).


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)

Sphere formation of the ALDHhigh and ALDHlow cells.A total of 10,000 isolated ALDHhigh or ALDHlow cells were cultured in serum-free medium. The representative photographs from the ALDHhigh cells (A) and ALDHlow cells (B) were taken on day 14. The ALDHhigh cells could form much more spheres than the ALDHlow H460 cells (C). The number of spheres were expressed as Mean± SEM, n = 4.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0103193-g002: Sphere formation of the ALDHhigh and ALDHlow cells.A total of 10,000 isolated ALDHhigh or ALDHlow cells were cultured in serum-free medium. The representative photographs from the ALDHhigh cells (A) and ALDHlow cells (B) were taken on day 14. The ALDHhigh cells could form much more spheres than the ALDHlow H460 cells (C). The number of spheres were expressed as Mean± SEM, n = 4.
Mentions: CSCs are characterized by their sphere formation ability, tumorigenesis and self-renewal. To verify whether the ALDEFLUOR-enriched population contained cancer stem cell-like cells, we first performed the sphere formation assay by culturing the ALDHhigh cells in serum-free medium; the ALDHlow cells were also cultured under these conditions and were used as a negative control. Compared to the ALDHlow cells, the ALDHhigh cells had an enhanced sphere forming ability. Figure 2A and B show representative pictures from the ALDHhigh and ALDHlow cells on day 14. We also counted the numbers of the spheres formed by ALDHhigh or ALDHlow H460 cells. As shown in Figure 2C, compared to ALDHlow H460 cells, the enriched ALDHhigh H460 cells could form much more spheres (Figure 2C, P = 0.0034).

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