Cannabinoid receptor 2 plays a pro-tumorigenic role in non-small cell lung cancer by limiting anti-tumor activity of CD8+ T and NK cells
Cannabinoid (CB) receptors (CB1 and CB2) are expressed on cancer cells and their expression influences carcinogenesis in various tumor entities. Cells of the tumor microenvironment (TME) also express CB receptors, however, their role in tumor development is still unclear. We, therefore, investigated...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-01-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.997115/full |
| _version_ | 1797957470085185536 |
|---|---|
| author | Arailym Sarsembayeva Melanie Kienzl Eva Gruden Dusica Ristic Kathrin Maitz Paulina Valadez-Cosmes Ana Santiso Carina Hasenoehrl Luka Brcic Jörg Lindenmann Julia Kargl Rudolf Schicho Rudolf Schicho |
| author_facet | Arailym Sarsembayeva Melanie Kienzl Eva Gruden Dusica Ristic Kathrin Maitz Paulina Valadez-Cosmes Ana Santiso Carina Hasenoehrl Luka Brcic Jörg Lindenmann Julia Kargl Rudolf Schicho Rudolf Schicho |
| author_sort | Arailym Sarsembayeva |
| collection | DOAJ |
| description | Cannabinoid (CB) receptors (CB1 and CB2) are expressed on cancer cells and their expression influences carcinogenesis in various tumor entities. Cells of the tumor microenvironment (TME) also express CB receptors, however, their role in tumor development is still unclear. We, therefore, investigated the role of TME-derived CB1 and CB2 receptors in a model of non-small cell lung cancer (NSCLC). Leukocytes in the TME of mouse and human NSCLC express CB receptors, with CB2 showing higher expression than CB1. In the tumor model, using CB1- (CB1-/-) and CB2-knockout (CB2-/-) mice, only deficiency of CB2, but not of CB1, resulted in reduction of tumor burden vs. wild type (WT) littermates. This was accompanied by increased accumulation and tumoricidal activity of CD8+ T and natural killer cells, as well as increased expression of programmed death-1 (PD-1) and its ligand on lymphoid and myeloid cells, respectively. CB2-/- mice responded significantly better to anti-PD-1 therapy than WT mice. The treatment further increased infiltration of cytotoxic lymphocytes into the TME of CB2-/- mice. Our findings demonstrate that TME-derived CB2 dictates the immune cell recruitment into tumors and the responsiveness to anti-PD-1 therapy in a model of NSCLC. CB2 could serve as an adjuvant target for immunotherapy. |
| first_indexed | 2024-04-11T00:05:35Z |
| format | Article |
| id | doaj.art-8fc695dd4a07458a91b2e4e48bd4b41a |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-11T00:05:35Z |
| publishDate | 2023-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-8fc695dd4a07458a91b2e4e48bd4b41a2023-01-09T11:39:46ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-01-011310.3389/fimmu.2022.997115997115Cannabinoid receptor 2 plays a pro-tumorigenic role in non-small cell lung cancer by limiting anti-tumor activity of CD8+ T and NK cellsArailym Sarsembayeva0Melanie Kienzl1Eva Gruden2Dusica Ristic3Kathrin Maitz4Paulina Valadez-Cosmes5Ana Santiso6Carina Hasenoehrl7Luka Brcic8Jörg Lindenmann9Julia Kargl10Rudolf Schicho11Rudolf Schicho12Division of Pharmacology, Otto Loewi Research Center, Medical University of Graz, Graz, AustriaDivision of Pharmacology, Otto Loewi Research Center, Medical University of Graz, Graz, AustriaDivision of Pharmacology, Otto Loewi Research Center, Medical University of Graz, Graz, AustriaDivision of Pharmacology, Otto Loewi Research Center, Medical University of Graz, Graz, AustriaDivision of Pharmacology, Otto Loewi Research Center, Medical University of Graz, Graz, AustriaDivision of Pharmacology, Otto Loewi Research Center, Medical University of Graz, Graz, AustriaDivision of Pharmacology, Otto Loewi Research Center, Medical University of Graz, Graz, AustriaDivision of Pharmacology, Otto Loewi Research Center, Medical University of Graz, Graz, AustriaDiagnostic and Research Institute of Pathology, Medical University of Graz, Graz, AustriaDivision of Thoracic and Hyperbaric Surgery, Department of Surgery, Medical University of Graz, Graz, AustriaDivision of Pharmacology, Otto Loewi Research Center, Medical University of Graz, Graz, AustriaDivision of Pharmacology, Otto Loewi Research Center, Medical University of Graz, Graz, AustriaBioTechMed, Graz, AustriaCannabinoid (CB) receptors (CB1 and CB2) are expressed on cancer cells and their expression influences carcinogenesis in various tumor entities. Cells of the tumor microenvironment (TME) also express CB receptors, however, their role in tumor development is still unclear. We, therefore, investigated the role of TME-derived CB1 and CB2 receptors in a model of non-small cell lung cancer (NSCLC). Leukocytes in the TME of mouse and human NSCLC express CB receptors, with CB2 showing higher expression than CB1. In the tumor model, using CB1- (CB1-/-) and CB2-knockout (CB2-/-) mice, only deficiency of CB2, but not of CB1, resulted in reduction of tumor burden vs. wild type (WT) littermates. This was accompanied by increased accumulation and tumoricidal activity of CD8+ T and natural killer cells, as well as increased expression of programmed death-1 (PD-1) and its ligand on lymphoid and myeloid cells, respectively. CB2-/- mice responded significantly better to anti-PD-1 therapy than WT mice. The treatment further increased infiltration of cytotoxic lymphocytes into the TME of CB2-/- mice. Our findings demonstrate that TME-derived CB2 dictates the immune cell recruitment into tumors and the responsiveness to anti-PD-1 therapy in a model of NSCLC. CB2 could serve as an adjuvant target for immunotherapy.https://www.frontiersin.org/articles/10.3389/fimmu.2022.997115/fullCB1CB2cannabinoid receptorsnon-small cell lung cancertumor microenvironmentCD8+ T cells |
| spellingShingle | Arailym Sarsembayeva Melanie Kienzl Eva Gruden Dusica Ristic Kathrin Maitz Paulina Valadez-Cosmes Ana Santiso Carina Hasenoehrl Luka Brcic Jörg Lindenmann Julia Kargl Rudolf Schicho Rudolf Schicho Cannabinoid receptor 2 plays a pro-tumorigenic role in non-small cell lung cancer by limiting anti-tumor activity of CD8+ T and NK cells Frontiers in Immunology CB1 CB2 cannabinoid receptors non-small cell lung cancer tumor microenvironment CD8+ T cells |
| title | Cannabinoid receptor 2 plays a pro-tumorigenic role in non-small cell lung cancer by limiting anti-tumor activity of CD8+ T and NK cells |
| title_full | Cannabinoid receptor 2 plays a pro-tumorigenic role in non-small cell lung cancer by limiting anti-tumor activity of CD8+ T and NK cells |
| title_fullStr | Cannabinoid receptor 2 plays a pro-tumorigenic role in non-small cell lung cancer by limiting anti-tumor activity of CD8+ T and NK cells |
| title_full_unstemmed | Cannabinoid receptor 2 plays a pro-tumorigenic role in non-small cell lung cancer by limiting anti-tumor activity of CD8+ T and NK cells |
| title_short | Cannabinoid receptor 2 plays a pro-tumorigenic role in non-small cell lung cancer by limiting anti-tumor activity of CD8+ T and NK cells |
| title_sort | cannabinoid receptor 2 plays a pro tumorigenic role in non small cell lung cancer by limiting anti tumor activity of cd8 t and nk cells |
| topic | CB1 CB2 cannabinoid receptors non-small cell lung cancer tumor microenvironment CD8+ T cells |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.997115/full |
| work_keys_str_mv | AT arailymsarsembayeva cannabinoidreceptor2playsaprotumorigenicroleinnonsmallcelllungcancerbylimitingantitumoractivityofcd8tandnkcells AT melaniekienzl cannabinoidreceptor2playsaprotumorigenicroleinnonsmallcelllungcancerbylimitingantitumoractivityofcd8tandnkcells AT evagruden cannabinoidreceptor2playsaprotumorigenicroleinnonsmallcelllungcancerbylimitingantitumoractivityofcd8tandnkcells AT dusicaristic cannabinoidreceptor2playsaprotumorigenicroleinnonsmallcelllungcancerbylimitingantitumoractivityofcd8tandnkcells AT kathrinmaitz cannabinoidreceptor2playsaprotumorigenicroleinnonsmallcelllungcancerbylimitingantitumoractivityofcd8tandnkcells AT paulinavaladezcosmes cannabinoidreceptor2playsaprotumorigenicroleinnonsmallcelllungcancerbylimitingantitumoractivityofcd8tandnkcells AT anasantiso cannabinoidreceptor2playsaprotumorigenicroleinnonsmallcelllungcancerbylimitingantitumoractivityofcd8tandnkcells AT carinahasenoehrl cannabinoidreceptor2playsaprotumorigenicroleinnonsmallcelllungcancerbylimitingantitumoractivityofcd8tandnkcells AT lukabrcic cannabinoidreceptor2playsaprotumorigenicroleinnonsmallcelllungcancerbylimitingantitumoractivityofcd8tandnkcells AT jorglindenmann cannabinoidreceptor2playsaprotumorigenicroleinnonsmallcelllungcancerbylimitingantitumoractivityofcd8tandnkcells AT juliakargl cannabinoidreceptor2playsaprotumorigenicroleinnonsmallcelllungcancerbylimitingantitumoractivityofcd8tandnkcells AT rudolfschicho cannabinoidreceptor2playsaprotumorigenicroleinnonsmallcelllungcancerbylimitingantitumoractivityofcd8tandnkcells AT rudolfschicho cannabinoidreceptor2playsaprotumorigenicroleinnonsmallcelllungcancerbylimitingantitumoractivityofcd8tandnkcells |