Enhanced anti‐tumor effects of the PD‐1 blockade combined with a highly absorptive form of curcumin targeting STAT3

Autor: Tomonori Yaguchi, Taeko Hayakawa, Yutaka Kawakami
Rok vydání: 2020
Předmět:
0301 basic medicine
Cancer Research
T-Lymphocytes
medicine.medical_treatment
STAT3
Mice
chemistry.chemical_compound
Basic and Clinical Immunology
0302 clinical medicine
Nude mouse
Cancer immunotherapy
Neoplasms
Immune Checkpoint Inhibitors
Mice
Inbred BALB C
biology
Chemistry
NF-kappa B
General Medicine
medicine.anatomical_structure
Oncology
030220 oncology & carcinogenesis
Drug Therapy
Combination
Female
Original Article
Immunotherapy
PD‐1/PD‐L1 blockade
STAT3 Transcription Factor
Curcumin
T cell
Mice
Nude
Antineoplastic Agents
Interferon-gamma
03 medical and health sciences
Immune system
Antigen
medicine
Animals
Humans
dendritic cells
cancer immunotherapy
Interleukin-6
Plant Extracts
Original Articles
biology.organism_classification
Mice
Inbred C57BL
030104 developmental biology
Cancer cell
Cancer research
Zdroj: Cancer Science
ISSN: 1349-7006
1347-9032
DOI: 10.1111/cas.14675
Popis: PD‐1/PD‐L1 immune checkpoint inhibitors are promising cancer immunotherapies however responses are still limited and the development of more effective combination immunotherapy is needed. We previously reported that STAT3 activation in cancer cells and immune cells was involved in immune‐resistant mechanisms. In this study, we evaluated the effect of highly absorptive forms of curcumin extracts and synthetic curcumin on anti‐tumor T cell responses. The curcumin po administration resulted in the significant augmentation of in vivo induction of tumor antigen‐specific T cells through restoration of dendritic cells (DCs) by inhibiting directly STAT3 in DCs and indirectly via reduced IL‐6 production from STAT3 activated cancer cells in 2 syngeneic MC38 and CT26 murine tumor models. Curcumin also showed direct DC enhancing activity and enhanced T cell induction for the immunized antigens in non‐tumor‐bearing mice and human hosts. Curcumin restored DC functions in xenogeneic nude mouse model implanted with high IL‐6‐producing human clear cell ovarian cancer cells. The combination of curcumin and PD‐1/PD‐L1 Abs demonstrated a synergistic anti‐tumor activity in MC38 murine tumor models. These results indicated that curcumin augments the induction of tumor antigen‐specific T cells by restoring the T cell stimulatory activity of DCs targeting activated STAT3 in both cancer cells and immune cells. Combination immunotherapy with curcumin and PD‐1/PD‐L1 Ab is an attractive strategy in the development of effective immunotherapy against various cancers.
Highly absorptive form of curcumin can restore the T cell stimulatory activity of DCs and augment the induction of tumor antigen‐specific T cells by targeting activated STAT3 in both cancer cells and immune cells. Combination immunotherapy with curcumin and PD‐1/PD‐L1 Ab is an attractive strategy in the development of effective immunotherapy against various cancers.
Databáze: OpenAIRE
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