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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

The identification of ALDHhigh cells from the human non-small cell lung cancer cells and primary tumor cells.ALDEFLUOR was used as a single marker to identify the ALDHhigh cells from the H460 cell line (A) and freshly harvested tumor cells (B). Tumor cells incubated with both ALDH and DEAB were used as a negative control.
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pone-0103193-g001: The identification of ALDHhigh cells from the human non-small cell lung cancer cells and primary tumor cells.ALDEFLUOR was used as a single marker to identify the ALDHhigh cells from the H460 cell line (A) and freshly harvested tumor cells (B). Tumor cells incubated with both ALDH and DEAB were used as a negative control.

Mentions: ALDEFLUOR/ALDH has been generally used as a single marker to identify cancer stem cells from both human and murine tumors, such as melanoma and breast cancers [20], [23]. By performing this technique, an enriched CSC population was isolated from the human lung cancer cell line H460. As shown in Figure 1A, approximately 10% of the tumor cells were ALDHhigh. The remaining 90% of the cells belonged to the ALDHlow population. Using a flow cytometry sorting technique, we isolated an equal percentage of ALDHhigh cells and ALDHlow cells to further verify the cancer stem cell characteristics of the enriched ALDHhigh population. Similarly, the presence of the ALDHhigh subpopulation cells in established murine tumors was confirmed by analyzing freshly harvested tumor cells from in vivo established H460 murine tumors. After being digested into single cell suspensions, the ALDEFLUOR assay and flow cytometry were performed to verify the activity of ALDH in the xenograft. As shown in Figure 1B, around 6% of the freshly harvested tumor cells were the ALDHhigh subpopulation.


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)

The identification of ALDHhigh cells from the human non-small cell lung cancer cells and primary tumor cells.ALDEFLUOR was used as a single marker to identify the ALDHhigh cells from the H460 cell line (A) and freshly harvested tumor cells (B). Tumor cells incubated with both ALDH and DEAB were used as a negative control.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0103193-g001: The identification of ALDHhigh cells from the human non-small cell lung cancer cells and primary tumor cells.ALDEFLUOR was used as a single marker to identify the ALDHhigh cells from the H460 cell line (A) and freshly harvested tumor cells (B). Tumor cells incubated with both ALDH and DEAB were used as a negative control.
Mentions: ALDEFLUOR/ALDH has been generally used as a single marker to identify cancer stem cells from both human and murine tumors, such as melanoma and breast cancers [20], [23]. By performing this technique, an enriched CSC population was isolated from the human lung cancer cell line H460. As shown in Figure 1A, approximately 10% of the tumor cells were ALDHhigh. The remaining 90% of the cells belonged to the ALDHlow population. Using a flow cytometry sorting technique, we isolated an equal percentage of ALDHhigh cells and ALDHlow cells to further verify the cancer stem cell characteristics of the enriched ALDHhigh population. Similarly, the presence of the ALDHhigh subpopulation cells in established murine tumors was confirmed by analyzing freshly harvested tumor cells from in vivo established H460 murine tumors. After being digested into single cell suspensions, the ALDEFLUOR assay and flow cytometry were performed to verify the activity of ALDH in the xenograft. As shown in Figure 1B, around 6% of the freshly harvested tumor cells were the ALDHhigh subpopulation.

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