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ATP-dependent recruitment, survival and differentiation of dendritic cell precursors in the tumor bed after anticancer chemotherapy.

Ma Y, Adjemian S, Yang H, Catani JP, Hannani D, Martins I, Michaud M, Kepp O, Sukkurwala AQ, Vacchelli E, Galluzzi L, Zitvogel L, Kroemer G - Oncoimmunology (2013)

Bottom Line: Tumor cells succumb to chemotherapy while releasing ATP.We have found that extracellular ATP attracts dendritic cell (DC) precursors into the tumor bed, facilitates their permanence in the proximity of dying cells and promotes their differentiation into mature DCs endowed with the capacity of presenting tumor-associated antigens.

View Article: PubMed Central - PubMed

Affiliation: INSERM, U848; Villejuif, France ; Institut Gustave Roussy; Villejuif, France ; Université Paris Sud/Paris XI; Le Kremlin Bicêtre; Paris, France.

ABSTRACT
Tumor cells succumb to chemotherapy while releasing ATP. We have found that extracellular ATP attracts dendritic cell (DC) precursors into the tumor bed, facilitates their permanence in the proximity of dying cells and promotes their differentiation into mature DCs endowed with the capacity of presenting tumor-associated antigens.

No MeSH data available.


Related in: MedlinePlus

Figure 1. Multipronged activity of extracellular ATP during immunogenic chemotherapy. Besides emitting other immunogenic signals, cancer cells succumbing to anthracyclines actively secrete ATP in an autophagy-dependent manner. In turn, extracellular ATP (1) operates as a potent chemotactic factor to favor the local recruitment of distinct populations of myeloid cells, (2) functions as a trophic factor, allowing for the survival and persistence of myeloid cells in the proximity of dying cancer cells and (3) skews the default differentiation pathway of myeloid cells toward the generation of mature inflammatory dendritic cells (DCs), which exert potent antigen-presenting functions. [ATP]Extra, extracellular ATP concentration.
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Figure 1: Figure 1. Multipronged activity of extracellular ATP during immunogenic chemotherapy. Besides emitting other immunogenic signals, cancer cells succumbing to anthracyclines actively secrete ATP in an autophagy-dependent manner. In turn, extracellular ATP (1) operates as a potent chemotactic factor to favor the local recruitment of distinct populations of myeloid cells, (2) functions as a trophic factor, allowing for the survival and persistence of myeloid cells in the proximity of dying cancer cells and (3) skews the default differentiation pathway of myeloid cells toward the generation of mature inflammatory dendritic cells (DCs), which exert potent antigen-presenting functions. [ATP]Extra, extracellular ATP concentration.

Mentions: Based on these results, we hypothesize that extracellular ATP may exert three distinct effects on the immune infiltrate following immunogenic chemotherapy (Fig. 1). First, ATP is certainly one of the most important chemotactic factors that bridge cell death to the recruitment of a range of immune effector cells, including DCs and their precursors. Second, ATP may serve as a trophic factor to maintain DCs (and/or their precursors) in the proximity of stressed and dying cancer cells. Third, ATP drives the differentiation of DC precursors into mature antigen-presenting cells exhibiting an immunophenotype similar to that of inflammatory DCs.10 Thus, manipulations designed to preserve the intratumoral levels of ATP, such as the inhibition of ecto-ATPases, may enhance antitumor immune responses by a multipronged positive effect on the recruitment, permanence and differentiation of DC precursors.


ATP-dependent recruitment, survival and differentiation of dendritic cell precursors in the tumor bed after anticancer chemotherapy.

Ma Y, Adjemian S, Yang H, Catani JP, Hannani D, Martins I, Michaud M, Kepp O, Sukkurwala AQ, Vacchelli E, Galluzzi L, Zitvogel L, Kroemer G - Oncoimmunology (2013)

Figure 1. Multipronged activity of extracellular ATP during immunogenic chemotherapy. Besides emitting other immunogenic signals, cancer cells succumbing to anthracyclines actively secrete ATP in an autophagy-dependent manner. In turn, extracellular ATP (1) operates as a potent chemotactic factor to favor the local recruitment of distinct populations of myeloid cells, (2) functions as a trophic factor, allowing for the survival and persistence of myeloid cells in the proximity of dying cancer cells and (3) skews the default differentiation pathway of myeloid cells toward the generation of mature inflammatory dendritic cells (DCs), which exert potent antigen-presenting functions. [ATP]Extra, extracellular ATP concentration.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3716753&req=5

Figure 1: Figure 1. Multipronged activity of extracellular ATP during immunogenic chemotherapy. Besides emitting other immunogenic signals, cancer cells succumbing to anthracyclines actively secrete ATP in an autophagy-dependent manner. In turn, extracellular ATP (1) operates as a potent chemotactic factor to favor the local recruitment of distinct populations of myeloid cells, (2) functions as a trophic factor, allowing for the survival and persistence of myeloid cells in the proximity of dying cancer cells and (3) skews the default differentiation pathway of myeloid cells toward the generation of mature inflammatory dendritic cells (DCs), which exert potent antigen-presenting functions. [ATP]Extra, extracellular ATP concentration.
Mentions: Based on these results, we hypothesize that extracellular ATP may exert three distinct effects on the immune infiltrate following immunogenic chemotherapy (Fig. 1). First, ATP is certainly one of the most important chemotactic factors that bridge cell death to the recruitment of a range of immune effector cells, including DCs and their precursors. Second, ATP may serve as a trophic factor to maintain DCs (and/or their precursors) in the proximity of stressed and dying cancer cells. Third, ATP drives the differentiation of DC precursors into mature antigen-presenting cells exhibiting an immunophenotype similar to that of inflammatory DCs.10 Thus, manipulations designed to preserve the intratumoral levels of ATP, such as the inhibition of ecto-ATPases, may enhance antitumor immune responses by a multipronged positive effect on the recruitment, permanence and differentiation of DC precursors.

Bottom Line: Tumor cells succumb to chemotherapy while releasing ATP.We have found that extracellular ATP attracts dendritic cell (DC) precursors into the tumor bed, facilitates their permanence in the proximity of dying cells and promotes their differentiation into mature DCs endowed with the capacity of presenting tumor-associated antigens.

View Article: PubMed Central - PubMed

Affiliation: INSERM, U848; Villejuif, France ; Institut Gustave Roussy; Villejuif, France ; Université Paris Sud/Paris XI; Le Kremlin Bicêtre; Paris, France.

ABSTRACT
Tumor cells succumb to chemotherapy while releasing ATP. We have found that extracellular ATP attracts dendritic cell (DC) precursors into the tumor bed, facilitates their permanence in the proximity of dying cells and promotes their differentiation into mature DCs endowed with the capacity of presenting tumor-associated antigens.

No MeSH data available.


Related in: MedlinePlus