In:
The Journal of Immunology, The American Association of Immunologists, Vol. 204, No. 1_Supplement ( 2020-05-01), p. 240.10-240.10
Abstract:
One of the new therapeutic strategy to promote cancer free survival is to combine dietary intervention like fasting or fasting mimicking diets (FMDs) with cancer treatments. FMDs enhance the efficacy of a wide variety of therapies ranging from chemotherapy to kinase inhibitors to immunotherapy, weakening cancer cells while protecting normal cells and tissues. In this work we show that FMD in combination with vincristine (VC), enhance the death of acute lymphoblastic leukemia (ALL) by inhibition of autophagy and induction of apoptosis by p53 modulation and activation of caspase-3. Our data indicates that a periodic FMD increases the efficacy of VC and extends the cancer free survival of an in-vivo mouse syngeneic pre-B ALL model. We identify in human and mice leukemic cells that the autophagy inhibition is the mechanism used by FMD to potentiate the cytotoxic effect of VC. Finally, in vivo treatment of FMD+VC with an autophagy inhibitor shows a synergistic effect on increasing survival in ALL mice. Furthermore, FMD induces activation of anticancer immunity. The gene expression profile consistent with anti-cancer immune responses resulting from VC plus FMD together with accelerated cancer progression when these treatments were combined with anti-CD8 antibodies indicate a central role of the immune system in these effects. Thus, the inhibition of autophagy and enhancement of immune responses are responsible for the ability of FMD to promote cancer free survival in ALL mice.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.204.Supp.240.10
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2020
detail.hit.zdb_id:
1475085-5
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