PMID- 37758101
OWN - NLM
STAT- Publisher
LR  - 20231013
IS  - 1096-1186 (Electronic)
IS  - 1043-6618 (Linking)
VI  - 196
DP  - 2023 Oct
TI  - A sequential scheme including PTT and 2'3'-cGAMP/CQ-LP reveals the antitumor 
      immune function of PTT through the type I interferon pathway.
PG  - 106939
LID - S1043-6618(23)00295-5 [pii]
LID - 10.1016/j.phrs.2023.106939 [doi]
AB  - Photothermal therapy (PTT) is a promising antitumor treatment that is easy to 
      implement, minimally invasive, and precisely controllable, and evokes strong 
      antitumor immunity. We believe that a thorough elucidation of its underlying 
      antitumor immune mechanisms would contribute to the rational design of 
      combination treatments with other antitumor strategies and consequently 
      potentiate clinical use. In this study, PTT using indocyanine green (ICG) induced 
      STING-dependent type I interferon (IFN) production in macrophages (RAW264.7 and 
      bone marrow-derived macrophages (BMDMs)), as proven by the use of a STING 
      inhibitor (C178), and triggered STING-independent type I IFN generation in tumor 
      cells (CT26 and 4T1), which was inhibited by DNase pretreatment. A novel liposome 
      coloaded with the STING agonist 2'3'-cGAMP (cGAMP) and chloroquine (CQ) was 
      constructed to achieve synergistic effect with PTT, in which CQ increased cGAMP 
      entrapment efficiency and prevented STING degradation after IFN signaling 
      activation. The sequential combination treatment caused a significant increase in 
      tumor cell apoptosis, probably due to interferon stimulating gene products 15 and 
      54 (ISG15 and ISG 54), and achieved a more striking antitumor inhibition effect 
      in the CT26 tumor model than the 4T1 model, likely due to higher STAT1 expression 
      and consequently more intense IFN signal transduction. In the tumor 
      microenvironment, the combination treatment increased infiltrating CD8(+)T cells 
      (4-fold) and M1-like TAMs (10-fold), and decreased M-MDSCs (over 2-fold) and 
      M2-like TAMs (over 4-fold). Above all, in-depth exploration of the antitumor 
      mechanism of PTT provides guidance for selecting sensitive tumor models and 
      designing reasonable clinical schemes.
CI  - Copyright (c) 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.
FAU - Song, Xiaoshuang
AU  - Song X
AD  - Department of Biotherapy，Cancer Center and State Key Laboratory of 
      Biotherapy，West China Hospital, Sichuan University, Chengdu 610041, China.
FAU - Wang, Mao
AU  - Wang M
AD  - Department of Biotherapy，Cancer Center and State Key Laboratory of 
      Biotherapy，West China Hospital, Sichuan University, Chengdu 610041, China.
FAU - Liu, Simeng
AU  - Liu S
AD  - Department of Biotherapy，Cancer Center and State Key Laboratory of 
      Biotherapy，West China Hospital, Sichuan University, Chengdu 610041, China.
FAU - Liu, Huimin
AU  - Liu H
AD  - Department of Biotherapy，Cancer Center and State Key Laboratory of 
      Biotherapy，West China Hospital, Sichuan University, Chengdu 610041, China.
FAU - Jiang, Ailing
AU  - Jiang A
AD  - Department of Biotherapy，Cancer Center and State Key Laboratory of 
      Biotherapy，West China Hospital, Sichuan University, Chengdu 610041, China.
FAU - Zou, Yu
AU  - Zou Y
AD  - Department of Biotherapy，Cancer Center and State Key Laboratory of 
      Biotherapy，West China Hospital, Sichuan University, Chengdu 610041, China.
FAU - Deng, Yuchuan
AU  - Deng Y
AD  - Department of Biotherapy，Cancer Center and State Key Laboratory of 
      Biotherapy，West China Hospital, Sichuan University, Chengdu 610041, China.
FAU - Qin, Qin
AU  - Qin Q
AD  - Department of Biotherapy，Cancer Center and State Key Laboratory of 
      Biotherapy，West China Hospital, Sichuan University, Chengdu 610041, China.
FAU - Song, Yiran
AU  - Song Y
AD  - Department of Biotherapy，Cancer Center and State Key Laboratory of 
      Biotherapy，West China Hospital, Sichuan University, Chengdu 610041, China.
FAU - Zheng, Yu
AU  - Zheng Y
AD  - Department of Biotherapy，Cancer Center and State Key Laboratory of 
      Biotherapy，West China Hospital, Sichuan University, Chengdu 610041, China. 
      Electronic address: zhengyu82@scu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20230925
PL  - Netherlands
TA  - Pharmacol Res
JT  - Pharmacological research
JID - 8907422
SB  - IM
OTO - NOTNLM
OT  - 2'3'-cGAMP
OT  - 2'3'-cGAMP (PubChem CID: 135564529)
OT  - C-178 (PubChem CID: 2866412)
OT  - Chloroquine
OT  - Chloroquine (PubChem CID: 2719)
OT  - ICG (PubChem CID: 11967809)
OT  - Photothermal therapy
OT  - STING-dependent
OT  - STING-independent
OT  - Type I interferon pathway
COIS- Declaration of Competing Interest Not applicable.
EDAT- 2023/09/28 00:42
MHDA- 2023/09/28 00:42
CRDT- 2023/09/27 19:16
PHST- 2023/05/19 00:00 [received]
PHST- 2023/09/22 00:00 [revised]
PHST- 2023/09/22 00:00 [accepted]
PHST- 2023/09/28 00:42 [pubmed]
PHST- 2023/09/28 00:42 [medline]
PHST- 2023/09/27 19:16 [entrez]
AID - S1043-6618(23)00295-5 [pii]
AID - 10.1016/j.phrs.2023.106939 [doi]
PST - ppublish
SO  - Pharmacol Res. 2023 Oct;196:106939. doi: 10.1016/j.phrs.2023.106939. Epub 2023 
      Sep 25.