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Immune-mediated tumor evolution: Nanog links the emergence of a stem like cancer cell state and immune evasion.

Mao CP, Wu T, Song KH, Kim TW - Oncoimmunology (2014)

Bottom Line: Tumor cells undergo molecular evolution under immune pressure.Using a murine metastatic lung cancer model, we recently reported that evolutionary pressure enforced through vaccination incites gain of Nanog, a master transcription factor that mediates both emergence of a stem-like cancer cell state and immune evasion.Thus, therapeutic strategies aiming to blunt NANOG's expression in patient tumors may improve the clinical management of cancer.

View Article: PubMed Central - PubMed

Affiliation: Departments of Pathology; Johns Hopkins School of Medicine ; Baltimore, MD USA.

ABSTRACT

Tumor cells undergo molecular evolution under immune pressure. Using a murine metastatic lung cancer model, we recently reported that evolutionary pressure enforced through vaccination incites gain of Nanog, a master transcription factor that mediates both emergence of a stem-like cancer cell state and immune evasion. Thus, therapeutic strategies aiming to blunt NANOG's expression in patient tumors may improve the clinical management of cancer.

No MeSH data available.


Related in: MedlinePlus

Vaccination-mediated selection and enrichment of Nanog+ tumor cells resistant to antigen-specific cytotoxic T lymphocytes. In this model, the tumor initially comprises a major population of Nanog− cells and a minor population of Nanog+ cells. Immune selection—first instigated by natural host immunosurveillance and then reinforced by vaccination—drives the preferential survival and expansion of the cytotoxic T lymphocyte (CTL)-resistant Nanog+ cancer cells. These Nanog+ malignant cells, in turn, mediate the immune-resistant and stem-like phenotype of the tumor and drive therapeutic failure and disease progression.
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f0001: Vaccination-mediated selection and enrichment of Nanog+ tumor cells resistant to antigen-specific cytotoxic T lymphocytes. In this model, the tumor initially comprises a major population of Nanog− cells and a minor population of Nanog+ cells. Immune selection—first instigated by natural host immunosurveillance and then reinforced by vaccination—drives the preferential survival and expansion of the cytotoxic T lymphocyte (CTL)-resistant Nanog+ cancer cells. These Nanog+ malignant cells, in turn, mediate the immune-resistant and stem-like phenotype of the tumor and drive therapeutic failure and disease progression.

Mentions: Considering its role in maintenance of pluripotency, we reasoned that Nanog could contribute to the stem-like state of tumor cells remaining after immune selection. To test this premise, we silenced Nanog expression in P3 cells with siRNA and found that this Nanog knockdown reversed the stem-like state. In other words, the Nanog-depleted tumor cells lost each of the cardinal features of stem cells mentioned above, such as sphere formation and tumorigenicity.3 Conversely, when we introduced Nanog cDNA into P0 tumor cells, they acquired a stem-like state.3 These data clearly implicate a role for Nanog in the control of tumor stemness, but—perhaps more crucially—they also demonstrate that immune selection may modulate the expression of key pluripotency factors in the tumor and therefore delineate a link between emergence of a stem-like state in the tumor and immune escape (Fig. 1).


Immune-mediated tumor evolution: Nanog links the emergence of a stem like cancer cell state and immune evasion.

Mao CP, Wu T, Song KH, Kim TW - Oncoimmunology (2014)

Vaccination-mediated selection and enrichment of Nanog+ tumor cells resistant to antigen-specific cytotoxic T lymphocytes. In this model, the tumor initially comprises a major population of Nanog− cells and a minor population of Nanog+ cells. Immune selection—first instigated by natural host immunosurveillance and then reinforced by vaccination—drives the preferential survival and expansion of the cytotoxic T lymphocyte (CTL)-resistant Nanog+ cancer cells. These Nanog+ malignant cells, in turn, mediate the immune-resistant and stem-like phenotype of the tumor and drive therapeutic failure and disease progression.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4292413&req=5

f0001: Vaccination-mediated selection and enrichment of Nanog+ tumor cells resistant to antigen-specific cytotoxic T lymphocytes. In this model, the tumor initially comprises a major population of Nanog− cells and a minor population of Nanog+ cells. Immune selection—first instigated by natural host immunosurveillance and then reinforced by vaccination—drives the preferential survival and expansion of the cytotoxic T lymphocyte (CTL)-resistant Nanog+ cancer cells. These Nanog+ malignant cells, in turn, mediate the immune-resistant and stem-like phenotype of the tumor and drive therapeutic failure and disease progression.
Mentions: Considering its role in maintenance of pluripotency, we reasoned that Nanog could contribute to the stem-like state of tumor cells remaining after immune selection. To test this premise, we silenced Nanog expression in P3 cells with siRNA and found that this Nanog knockdown reversed the stem-like state. In other words, the Nanog-depleted tumor cells lost each of the cardinal features of stem cells mentioned above, such as sphere formation and tumorigenicity.3 Conversely, when we introduced Nanog cDNA into P0 tumor cells, they acquired a stem-like state.3 These data clearly implicate a role for Nanog in the control of tumor stemness, but—perhaps more crucially—they also demonstrate that immune selection may modulate the expression of key pluripotency factors in the tumor and therefore delineate a link between emergence of a stem-like state in the tumor and immune escape (Fig. 1).

Bottom Line: Tumor cells undergo molecular evolution under immune pressure.Using a murine metastatic lung cancer model, we recently reported that evolutionary pressure enforced through vaccination incites gain of Nanog, a master transcription factor that mediates both emergence of a stem-like cancer cell state and immune evasion.Thus, therapeutic strategies aiming to blunt NANOG's expression in patient tumors may improve the clinical management of cancer.

View Article: PubMed Central - PubMed

Affiliation: Departments of Pathology; Johns Hopkins School of Medicine ; Baltimore, MD USA.

ABSTRACT

Tumor cells undergo molecular evolution under immune pressure. Using a murine metastatic lung cancer model, we recently reported that evolutionary pressure enforced through vaccination incites gain of Nanog, a master transcription factor that mediates both emergence of a stem-like cancer cell state and immune evasion. Thus, therapeutic strategies aiming to blunt NANOG's expression in patient tumors may improve the clinical management of cancer.

No MeSH data available.


Related in: MedlinePlus