Inhibitory effect of adenosine on adaptive antitumor immunity and intervention strategies
Tumors in which the microenvironment is characterized by lack of immune cell infiltration are referred as "cold tumors" and typically exhibit low responsiveness to immune therapy. Targeting the factors contributing to "cold tumors" formation and converting them into "hot tumors" is a novel strategy for improving the efficacy of immunotherapy. Adenosine, a hydrolysis product of ATP, accumulates with a significantly higher concentration in the tumor microenvironments compared with normal tissue and exerts inhibitory effects on tumor-specific adaptive immunity. Tumor cells, dendritic cells, macrophages, and T cells express abundant adenosine receptors on their surfaces. The binding of adenosine to these receptors initiates downstream signaling pathways that suppress tumor antigen presentation and immune cell activation, consequently dampening adaptive immune responses against tumors. Adenosine down-regulates the expression of major histocompatibility complex Ⅱ and co-stimulatory factors on dendritic cells and macrophages, thereby inhibiting antigen presentation to T cells. Adenosine also inhibits ligand-receptor binding and transmembrane signaling on T cells, concomitantly suppressing the secretion of anti-tumor cytokines and impairing T cell activation. Furthermore, adenosine hinders effector T cell trafficking to tumor sites and infiltration by inhibiting chemokine secretion and KCa3.1 channels. Additionally, adenosine promotes the secretion of immunosuppressive cytokines, increases immune checkpoint protein expression, and enhances the activity of immunosuppressive cells, collectively curbing cytotoxic T cell-mediated tumor cell killing. Given the immunosuppressive role of adenosine in adaptive antitumor immunity, several inhibitors targeting adenosine generation or adenosine receptor blockade are currently in preclinical or clinical development with the aim of enhancing the effectiveness of immunotherapies. This review provides an overview of the inhibitory effects of adenosine on adaptive antitumor immunity, elucidate the molecular mechanisms involved, and summarizes the latest advances in application of adenosine inhibition strategies for antitumor immunotherapy.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:52 |
|---|---|
| Enthalten in: |
Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences - 52(2023), 5 vom: 26. Sept., Seite 567-577 |
| Sprache: |
Englisch |
|---|
| Weiterer Titel: |
腺苷对肿瘤获得性免疫的抑制作用及干预策略 |
|---|
| Beteiligte Personen: |
Wang, Longsheng [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Adenosine |
|---|
| Anmerkungen: |
Date Completed 03.11.2023 Date Revised 10.11.2023 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.3724/zdxbyxb-2023-0263 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM364082011 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM364082011 | ||
| 003 | DE-627 | ||
| 005 | 20231226094709.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3724/zdxbyxb-2023-0263 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1213.xml |
| 035 | |a (DE-627)NLM364082011 | ||
| 035 | |a (NLM)37916308 | ||
| 035 | |a (PII)1008-9292(2023)05-0567-11 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Wang, Longsheng |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Inhibitory effect of adenosine on adaptive antitumor immunity and intervention strategies |
| 246 | 3 | 3 | |a 腺苷对肿瘤获得性免疫的抑制作用及干预策略 |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 03.11.2023 | ||
| 500 | |a Date Revised 10.11.2023 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Tumors in which the microenvironment is characterized by lack of immune cell infiltration are referred as "cold tumors" and typically exhibit low responsiveness to immune therapy. Targeting the factors contributing to "cold tumors" formation and converting them into "hot tumors" is a novel strategy for improving the efficacy of immunotherapy. Adenosine, a hydrolysis product of ATP, accumulates with a significantly higher concentration in the tumor microenvironments compared with normal tissue and exerts inhibitory effects on tumor-specific adaptive immunity. Tumor cells, dendritic cells, macrophages, and T cells express abundant adenosine receptors on their surfaces. The binding of adenosine to these receptors initiates downstream signaling pathways that suppress tumor antigen presentation and immune cell activation, consequently dampening adaptive immune responses against tumors. Adenosine down-regulates the expression of major histocompatibility complex Ⅱ and co-stimulatory factors on dendritic cells and macrophages, thereby inhibiting antigen presentation to T cells. Adenosine also inhibits ligand-receptor binding and transmembrane signaling on T cells, concomitantly suppressing the secretion of anti-tumor cytokines and impairing T cell activation. Furthermore, adenosine hinders effector T cell trafficking to tumor sites and infiltration by inhibiting chemokine secretion and KCa3.1 channels. Additionally, adenosine promotes the secretion of immunosuppressive cytokines, increases immune checkpoint protein expression, and enhances the activity of immunosuppressive cells, collectively curbing cytotoxic T cell-mediated tumor cell killing. Given the immunosuppressive role of adenosine in adaptive antitumor immunity, several inhibitors targeting adenosine generation or adenosine receptor blockade are currently in preclinical or clinical development with the aim of enhancing the effectiveness of immunotherapies. This review provides an overview of the inhibitory effects of adenosine on adaptive antitumor immunity, elucidate the molecular mechanisms involved, and summarizes the latest advances in application of adenosine inhibition strategies for antitumor immunotherapy | ||
| 650 | 4 | |a Review | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Adenosine | |
| 650 | 4 | |a Immune suppression | |
| 650 | 4 | |a Review | |
| 650 | 4 | |a Targeting drug | |
| 650 | 4 | |a Tumor microenvironment | |
| 650 | 7 | |a Adenosine |2 NLM | |
| 650 | 7 | |a K72T3FS567 |2 NLM | |
| 650 | 7 | |a Cytokines |2 NLM | |
| 700 | 1 | |a Zhang, Wenxin |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Jie |e verfasserin |4 aut | |
| 700 | 1 | |a Zheng, Mingming |e verfasserin |4 aut | |
| 700 | 1 | |a Pan, Xiaohui |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Hongjie |e verfasserin |4 aut | |
| 700 | 1 | |a Ding, Ling |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences |d 2002 |g 52(2023), 5 vom: 26. Sept., Seite 567-577 |w (DE-627)NLM123207037 |x 1008-9292 |7 nnns |
| 773 | 1 | 8 | |g volume:52 |g year:2023 |g number:5 |g day:26 |g month:09 |g pages:567-577 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.3724/zdxbyxb-2023-0263 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 52 |j 2023 |e 5 |b 26 |c 09 |h 567-577 | ||