PMID- 38545099
OWN - NLM
STAT- MEDLINE
DCOM- 20240329
LR  - 20240514
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 15
DP  - 2024
TI  - LTX-315 triggers anticancer immunity by inducing MyD88-dependent maturation of 
      dendritic cells.
PG  - 1332922
LID - 10.3389/fimmu.2024.1332922 [doi]
LID - 1332922
AB  - LTX-315 is a synthetic cationic oncolytic peptide with potent anticancer activity 
      but limited toxicity for non-malignant cells. LTX-315 induces both immunogenic 
      tumor cell death and generation of tumor-specific immune responses in multiple 
      experimental tumor models. Given the central role of dendritic cell (DC) 
      maturation in the induction of antigen-specific immunity, we investigated the 
      effect of LTX-315 treatment on the maturation of tumor-infiltrating DCs (TiDCs) 
      and the generation of anti-melanoma immunity. We found that LTX-315 treatment 
      induces the maturation of DCs, both indirectly through the release of cancer 
      cell-derived damage-associated molecular patterns (DAMPs)/alarmins and nucleic 
      acids (DNA and RNA) capable of triggering distinct Toll-like receptor (TLR) 
      signaling, and, directly by activating TLR7. The latter results in the ignition 
      of multiple intracellular signaling pathways that promotes DC maturation, 
      including NF-kappaB, mitogen activated protein kinases (MAPKs), and inflammasome 
      signaling, as well as increased type 1 interferon production. Critically, the 
      effects of LTX-315 on DCs the consequent promotion of anti-melanoma immunity 
      depend on the cytosolic signal transducer myeloid differentiation response gene 
      88 (MyD88). These results cast light on the mechanisms by which LTX-315 induces 
      DC maturation and hence elicits anticancer immunity, with important implications 
      for the use of LTX-315 as an anticancer immunotherapeutic.
CI  - Copyright (c) 2024 Li, Yamazaki, He, Alam, Liu, Trivett, Sveinbjornsson, Rekdal, 
      Galluzzi, Oppenheim and Yang.
FAU - Li, Xiao-Qing
AU  - Li XQ
AD  - Department of Biochemistry and Molecular Biology, Tianjin Medical University 
      Cancer Institute and Hospital, National Clinical Research Center of Cancer, 
      Tianjin Medical University, Tianjin, China.
AD  - Laboratory of Cancer Innovation, Frederick National Laboratory for Cancer 
      Research, Center for Cancer Research, National Cancer Institute, Frederick, MD, 
      United States.
FAU - Yamazaki, Takahiro
AU  - Yamazaki T
AD  - Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, 
      United States.
FAU - He, Tianzhen
AU  - He T
AD  - Laboratory of Cancer Innovation, Frederick National Laboratory for Cancer 
      Research, Center for Cancer Research, National Cancer Institute, Frederick, MD, 
      United States.
FAU - Alam, Md Masud
AU  - Alam MM
AD  - Laboratory of Cancer Innovation, Frederick National Laboratory for Cancer 
      Research, Center for Cancer Research, National Cancer Institute, Frederick, MD, 
      United States.
FAU - Liu, Jia
AU  - Liu J
AD  - Laboratory of Cancer Innovation, Frederick National Laboratory for Cancer 
      Research, Center for Cancer Research, National Cancer Institute, Frederick, MD, 
      United States.
FAU - Trivett, Anna L
AU  - Trivett AL
AD  - Laboratory of Cancer Innovation, Frederick National Laboratory for Cancer 
      Research, Center for Cancer Research, National Cancer Institute, Frederick, MD, 
      United States.
FAU - Sveinbjornsson, Baldur
AU  - Sveinbjornsson B
AD  - Lytix Biopharma, Oslo, Norway.
FAU - Rekdal, Oystein
AU  - Rekdal O
AD  - Lytix Biopharma, Oslo, Norway.
FAU - Galluzzi, Lorenzo
AU  - Galluzzi L
AD  - Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, 
      United States.
AD  - Sandra and Edward Meyer Cancer Center, New York, NY, United States.
AD  - Caryl and Israel Englander Institute for Precision Medicine, New York, NY, United 
      States.
FAU - Oppenheim, Joost J
AU  - Oppenheim JJ
AD  - Laboratory of Cancer Innovation, Frederick National Laboratory for Cancer 
      Research, Center for Cancer Research, National Cancer Institute, Frederick, MD, 
      United States.
FAU - Yang, De
AU  - Yang D
AD  - Laboratory of Cancer Innovation, Frederick National Laboratory for Cancer 
      Research, Center for Cancer Research, National Cancer Institute, Frederick, MD, 
      United States.
LA  - eng
GR  - R01 CA271915/CA/NCI NIH HHS/United States
GR  - U54 CA274291/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20240313
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/metabolism
MH  - *Dendritic Cells
MH  - *Myeloid Differentiation Factor 88/metabolism
MH  - *Oligopeptides
MH  - Toll-Like Receptors/metabolism
PMC - PMC10967226
OTO - NOTNLM
OT  - LTX-315
OT  - MyD88
OT  - antitumor immunity
OT  - dendritic cells
OT  - melanoma
OT  - toll-like receptors
COIS- BS and OR are shareholders and employed by Lytix Biopharma. The remaining authors 
      declare that the research was conducted in the absence of any commercial or 
      financial relationships that could be construed as a potential conflict of 
      interest. The authors declare that this study received some funding from Lytix 
      Biopharma. As employees of Lytix Biopharma, BS and OR provided LTX-315 for this 
      study and assisted in reviewing & editing of the graphic abstract & manuscript.
EDAT- 2024/03/28 06:44
MHDA- 2024/03/29 06:45
PMCR- 2024/01/01
CRDT- 2024/03/28 04:03
PHST- 2023/11/03 00:00 [received]
PHST- 2024/02/22 00:00 [accepted]
PHST- 2024/03/29 06:45 [medline]
PHST- 2024/03/28 06:44 [pubmed]
PHST- 2024/03/28 04:03 [entrez]
PHST- 2024/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2024.1332922 [doi]
PST - epublish
SO  - Front Immunol. 2024 Mar 13;15:1332922. doi: 10.3389/fimmu.2024.1332922. 
      eCollection 2024.