4.5 Review

Targeting Treg cells in cancer immunotherapy

Journal

EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 49, Issue 8, Pages 1140-1146

Publisher

WILEY
DOI: 10.1002/eji.201847659

Keywords

CTLA-4; Foxp3; immunotherapy; regulatory T cells; tumor immunity

Categories

Funding

  1. Japan Society for the Promotion of Science [16H06295, 26253030, 26860331, 17K15723]
  2. Ministry of Education, Culture, Sports, Science and Technology of Japan [16H06295, 26253030]
  3. Core Research for Evolutional Science and Technology (CREST) from Japan Science and Technology Agency [17gm0410016h0006]
  4. Leading Advanced Projects for medical innovation (LEAP) from Japan Science and Technology Agency [18gm0010005h0001]
  5. Project for Cancer Research and Therapeutic Evolution (P-CREATE) by Japan Agency for Medical Research and Development [18cm0106303h0003]
  6. Grants-in-Aid for Scientific Research [17K15723, 26253030, 26860331, 16H06295] Funding Source: KAKEN

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Foxp3-expressing regulatory T (Treg) cells, which are indispensable for preventing autoimmunity, also suppress effective tumor immunity. Treg cells abundantly infiltrate into tumor tissues, which is often associated with poor prognosis in cancer patients. Removal of Treg cells enhances anti-tumor immune responses but may also elicit autoimmunity. A key issue in devising Treg-targeting cancer immunotherapy is, therefore, how to specifically deplete Treg cells infiltrating into tumor tissues without affecting tumor-reactive effector T cells, while suppressing autoimmunity. This can be achieved by differentially controlling Treg and effector T cells by various ways. In this review, we discuss how tumor-infiltrating Foxp3(+) Treg cells hamper effective anti-tumor immune responses especially in tumor tissues and how they can be specifically targeted for augmenting tumor immunity but not autoimmunity.

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