Lighting Up the Fire in the Microenvironment of Cold Tumors: A Major Challenge to Improve Cancer Immunotherapy
Immunotherapy includes immune checkpoint inhibitors (ICI) such as antibodies targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) or the programmed cell death protein/programmed death ligand 1 (PD-1/PD-L1) axis. Experimental and clinical evidence show that immunotherapy based on immune che...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-07-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/12/13/1787 |
| _version_ | 1797591878363774976 |
|---|---|
| author | Alice Benoit Guillaume Vogin Caroline Duhem Guy Berchem Bassam Janji |
| author_facet | Alice Benoit Guillaume Vogin Caroline Duhem Guy Berchem Bassam Janji |
| author_sort | Alice Benoit |
| collection | DOAJ |
| description | Immunotherapy includes immune checkpoint inhibitors (ICI) such as antibodies targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) or the programmed cell death protein/programmed death ligand 1 (PD-1/PD-L1) axis. Experimental and clinical evidence show that immunotherapy based on immune checkpoint inhibitors (ICI) provides long-term survival benefits to cancer patients in whom other conventional therapies have failed. However, only a minority of patients show high clinical benefits via the use of ICI alone. One of the major factors limiting the clinical benefits to ICI can be attributed to the lack of immune cell infiltration within the tumor microenvironment. Such tumors are classified as “cold/warm” or an immune “desert”; those displaying significant infiltration are considered “hot” or inflamed. This review will provide a brief summary of different tumor properties contributing to the establishment of cold tumors and describe major strategies that could reprogram non-inflamed cold tumors into inflamed hot tumors. More particularly, we will describe how targeting hypoxia can induce metabolic reprogramming that results in improving and extending the benefit of ICI. |
| first_indexed | 2024-03-11T01:44:47Z |
| format | Article |
| id | doaj.art-0cbb2baf83bf416d9c4c809f3a409b7b |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T01:44:47Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-0cbb2baf83bf416d9c4c809f3a409b7b2023-11-18T16:20:03ZengMDPI AGCells2073-44092023-07-011213178710.3390/cells12131787Lighting Up the Fire in the Microenvironment of Cold Tumors: A Major Challenge to Improve Cancer ImmunotherapyAlice Benoit0Guillaume Vogin1Caroline Duhem2Guy Berchem3Bassam Janji4Tumor Immunotherapy and Microenvironment (TIME) Group, Department of Cancer Research, Luxembourg Institute of Health (LIH), L-1210 Luxembourg, LuxembourgCentre National de Radiothérapie François Baclesse, L-4005 Esch-sur-Alzette, LuxembourgDepartment of Hemato-Oncology, Centre Hospitalier du Luxembourg, L-1210 Luxembourg, LuxembourgTumor Immunotherapy and Microenvironment (TIME) Group, Department of Cancer Research, Luxembourg Institute of Health (LIH), L-1210 Luxembourg, LuxembourgTumor Immunotherapy and Microenvironment (TIME) Group, Department of Cancer Research, Luxembourg Institute of Health (LIH), L-1210 Luxembourg, LuxembourgImmunotherapy includes immune checkpoint inhibitors (ICI) such as antibodies targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) or the programmed cell death protein/programmed death ligand 1 (PD-1/PD-L1) axis. Experimental and clinical evidence show that immunotherapy based on immune checkpoint inhibitors (ICI) provides long-term survival benefits to cancer patients in whom other conventional therapies have failed. However, only a minority of patients show high clinical benefits via the use of ICI alone. One of the major factors limiting the clinical benefits to ICI can be attributed to the lack of immune cell infiltration within the tumor microenvironment. Such tumors are classified as “cold/warm” or an immune “desert”; those displaying significant infiltration are considered “hot” or inflamed. This review will provide a brief summary of different tumor properties contributing to the establishment of cold tumors and describe major strategies that could reprogram non-inflamed cold tumors into inflamed hot tumors. More particularly, we will describe how targeting hypoxia can induce metabolic reprogramming that results in improving and extending the benefit of ICI.https://www.mdpi.com/2073-4409/12/13/1787immunotherapyimmune checkpoint inhibitorstumor microenvironmentmetabolic reprogramminghypoxia |
| spellingShingle | Alice Benoit Guillaume Vogin Caroline Duhem Guy Berchem Bassam Janji Lighting Up the Fire in the Microenvironment of Cold Tumors: A Major Challenge to Improve Cancer Immunotherapy Cells immunotherapy immune checkpoint inhibitors tumor microenvironment metabolic reprogramming hypoxia |
| title | Lighting Up the Fire in the Microenvironment of Cold Tumors: A Major Challenge to Improve Cancer Immunotherapy |
| title_full | Lighting Up the Fire in the Microenvironment of Cold Tumors: A Major Challenge to Improve Cancer Immunotherapy |
| title_fullStr | Lighting Up the Fire in the Microenvironment of Cold Tumors: A Major Challenge to Improve Cancer Immunotherapy |
| title_full_unstemmed | Lighting Up the Fire in the Microenvironment of Cold Tumors: A Major Challenge to Improve Cancer Immunotherapy |
| title_short | Lighting Up the Fire in the Microenvironment of Cold Tumors: A Major Challenge to Improve Cancer Immunotherapy |
| title_sort | lighting up the fire in the microenvironment of cold tumors a major challenge to improve cancer immunotherapy |
| topic | immunotherapy immune checkpoint inhibitors tumor microenvironment metabolic reprogramming hypoxia |
| url | https://www.mdpi.com/2073-4409/12/13/1787 |
| work_keys_str_mv | AT alicebenoit lightingupthefireinthemicroenvironmentofcoldtumorsamajorchallengetoimprovecancerimmunotherapy AT guillaumevogin lightingupthefireinthemicroenvironmentofcoldtumorsamajorchallengetoimprovecancerimmunotherapy AT carolineduhem lightingupthefireinthemicroenvironmentofcoldtumorsamajorchallengetoimprovecancerimmunotherapy AT guyberchem lightingupthefireinthemicroenvironmentofcoldtumorsamajorchallengetoimprovecancerimmunotherapy AT bassamjanji lightingupthefireinthemicroenvironmentofcoldtumorsamajorchallengetoimprovecancerimmunotherapy |