LAG3, TIM3 and TIGIT: New Targets for Immunotherapy and Potential Associations with Radiotherapy

The combination of immunotherapy and radiotherapy has demonstrated synergistic potential, especially when a combination of immune checkpoint inhibitors (ICIs) is administered. Cytotoxic T-Lymphocyte-Associated Protein-4 (CTLA-4) inhibitors and Programmed Death-Ligand 1 (PD-L1) inhibitors or Programm...

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Main Authors: Camil Ciprian Mireștean, Roxana Irina Iancu, Dragoș Petru Teodor Iancu
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:Current Oncology
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Online Access:https://www.mdpi.com/1718-7729/32/4/230
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author Camil Ciprian Mireștean
Roxana Irina Iancu
Dragoș Petru Teodor Iancu
author_facet Camil Ciprian Mireștean
Roxana Irina Iancu
Dragoș Petru Teodor Iancu
author_sort Camil Ciprian Mireștean
collection DOAJ
description The combination of immunotherapy and radiotherapy has demonstrated synergistic potential, especially when a combination of immune checkpoint inhibitors (ICIs) is administered. Cytotoxic T-Lymphocyte-Associated Protein-4 (CTLA-4) inhibitors and Programmed Death-Ligand 1 (PD-L1) inhibitors or Programmed Cell Death Protein 1 (PD-1) inhibitors have been assessed in both clinical and preclinical studies; the addition of radiotherapy activates immunomodulatory mechanisms materialized by an effect similar to “in situ” vaccination or the “abscopal” distant response of lesions outside the irradiation field. The new therapeutic targets (T cell immune-receptor with Ig and ITIM domains (TIGIT), Lymphocyte activating gene 3 (LAG-3), and T cell Ig- and mucin-domain-containing molecule-3 (TIM-3)) associated with traditional ICIs and radiotherapy open new perspectives to the concept of immuno-radiotherapy. The dynamic evaluation of T lymphocyte expression involved in the antitumor immune response, both in the tumor microenvironment (TME) and in the tumor itself, could have biomarker value in assessing the response to combination therapy with traditional and new ICIs in association with irradiation. Preclinical data justify the initiation of clinical trials in various tumor pathologies to explore this concept.
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issn 1198-0052
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series Current Oncology
spelling doaj-art-c2425d8cdabf44039a21daf8fa1e50372025-08-20T03:13:49ZengMDPI AGCurrent Oncology1198-00521718-77292025-04-0132423010.3390/curroncol32040230LAG3, TIM3 and TIGIT: New Targets for Immunotherapy and Potential Associations with RadiotherapyCamil Ciprian Mireștean0Roxana Irina Iancu1Dragoș Petru Teodor Iancu2Regional Institute of Oncology, 700483 Iasi, Romania“Gr. T. Popa” University of Medicine and Pharmacy, 700115 Iasi, RomaniaRegional Institute of Oncology, 700483 Iasi, RomaniaThe combination of immunotherapy and radiotherapy has demonstrated synergistic potential, especially when a combination of immune checkpoint inhibitors (ICIs) is administered. Cytotoxic T-Lymphocyte-Associated Protein-4 (CTLA-4) inhibitors and Programmed Death-Ligand 1 (PD-L1) inhibitors or Programmed Cell Death Protein 1 (PD-1) inhibitors have been assessed in both clinical and preclinical studies; the addition of radiotherapy activates immunomodulatory mechanisms materialized by an effect similar to “in situ” vaccination or the “abscopal” distant response of lesions outside the irradiation field. The new therapeutic targets (T cell immune-receptor with Ig and ITIM domains (TIGIT), Lymphocyte activating gene 3 (LAG-3), and T cell Ig- and mucin-domain-containing molecule-3 (TIM-3)) associated with traditional ICIs and radiotherapy open new perspectives to the concept of immuno-radiotherapy. The dynamic evaluation of T lymphocyte expression involved in the antitumor immune response, both in the tumor microenvironment (TME) and in the tumor itself, could have biomarker value in assessing the response to combination therapy with traditional and new ICIs in association with irradiation. Preclinical data justify the initiation of clinical trials in various tumor pathologies to explore this concept.https://www.mdpi.com/1718-7729/32/4/230radiotherapySRSimmunotherapyICIPD-1PD-L1
spellingShingle Camil Ciprian Mireștean
Roxana Irina Iancu
Dragoș Petru Teodor Iancu
LAG3, TIM3 and TIGIT: New Targets for Immunotherapy and Potential Associations with Radiotherapy
Current Oncology
radiotherapy
SRS
immunotherapy
ICI
PD-1
PD-L1
title LAG3, TIM3 and TIGIT: New Targets for Immunotherapy and Potential Associations with Radiotherapy
title_full LAG3, TIM3 and TIGIT: New Targets for Immunotherapy and Potential Associations with Radiotherapy
title_fullStr LAG3, TIM3 and TIGIT: New Targets for Immunotherapy and Potential Associations with Radiotherapy
title_full_unstemmed LAG3, TIM3 and TIGIT: New Targets for Immunotherapy and Potential Associations with Radiotherapy
title_short LAG3, TIM3 and TIGIT: New Targets for Immunotherapy and Potential Associations with Radiotherapy
title_sort lag3 tim3 and tigit new targets for immunotherapy and potential associations with radiotherapy
topic radiotherapy
SRS
immunotherapy
ICI
PD-1
PD-L1
url https://www.mdpi.com/1718-7729/32/4/230
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AT roxanairinaiancu lag3tim3andtigitnewtargetsforimmunotherapyandpotentialassociationswithradiotherapy
AT dragospetruteodoriancu lag3tim3andtigitnewtargetsforimmunotherapyandpotentialassociationswithradiotherapy