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Advancing with cancer immunotherapeutics: CD29+ regulatory T cell antagonism
  1. Francisco Javier Cubero1,2,
  2. Pablo Sarobe3,4,5,
  3. Gisa Tiegs6
  1. 1Immunology, Ophthalmology and ENT, Complutense University of Madrid Faculty of Medicine, Madrid, Spain
  2. 2Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain
  3. 3Centre for Biomedical Research, Network on Liver and Digestive Diseases(CIBEREHD), Madrid, Spain
  4. 4Programa de Inmunología e Inmunoterapia, Centro de Investigación MédicaAplicada (CIMA, CCUN), Universidad de Navarra, Pamplona, Spain
  5. 5IdiSNA, Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain
  6. 6Insitute of Experimental Immunology and Hepatology, University Medical Center, Hamburg, Germany
  1. Correspondence to Professor Gisa Tiegs, Insitute of Experimental Immunology and Hepatology, University Medical Center. Hamburg-Eppendorf. Germany, Hamburg, Germany; g.tiegs{at}

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During the past few decades, the field of immuno-oncology has evolved along with the development of novel immunotherapies targeting Foxp3-expressing regulatory T cells (Tregs), a distinctive lineage of CD4+ T cells, for patients with cancer. There is considerable experimental and clinical evidence to support the role of Tregs in tumour growth, progression and metastasis, thus favouring suppression of antitumor immune responses and, therefore, immune escape.1 However, its role in cancer is somehow controversial and continues to be studied in order to enlarge the few therapeutic options currently available for patients with metastatic cancer, the majority of which otherwise succumb to the disease.

As of today, the origin and phenotypic characteristics of Tregs remain elusive and so do the mechanisms governing their diversity of functions. To add more fuel to the fire, Tregs possess remarkable adaptability to their local environment and facilitate immune homeostasis through highly specialised tissue-specific pathways.2

In the context of liver metastasis, knowledge of Tregs originated from observations of primary liver cancers, including hepatocellular carcinoma (HCC).3 In fact, liver-derived Tregs are reportedly capable of suppressing both local and extrahepatic antitumour immunity. For cancers where immune checkpoint inhibitors (ICIs) are effective and routinely used, such as melanoma, lung cancer, urothelial and kidney cancers, liver metastasis was associated with a significantly lower response rate to ICI and overall worse survival.4–6

While most of the studies have focused on the role of …

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  • Collaborators N/A.

  • Contributors FJC, PS and GT contributed equally in the writing of the commentary.

  • Funding This work was supported by the MICINN Retos PID2020-117941RB-I00 all of which were cofinanced with Fondos FEDER, EXOHEP2-CM (S2022/BMD-7409), HORIZON-HLTH-2022-STAYHLTH-02 under agreement No 101095679, Instituto de Salud Carlos III (ISCIII) through the project 'PI20/00260' and cofunded by the European Union and FEDER, Gobierno de Navarra (grant GNS_54–2021), the Deutsche Forschungsgemeinschaft (DFG) grant TI 169/12-2 and CRC 1192 project A2.

  • Competing interests None declared.

  • Provenance and peer review Commissioned; internally peer reviewed.

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