CD6 and Its Interacting Partners: Newcomers to the Block of Cancer Immunotherapies

Int J Mol Sci. 2023 Dec 15;24(24):17510. doi: 10.3390/ijms242417510.

Abstract

Cancer management still requires more potent and safer treatments, of which immunomodulatory receptors on the lymphocyte surface have started to show promise in new cancer immunotherapies (e.g., CTLA-4 and PD-1). CD6 is a signal-transducing transmembrane receptor, mainly expressed by all T cells and some B and NK cell subsets, whose endogenous ligands (CD166/ALCAM, CD318/CDCP-1, Galectins 1 and 3) are overexpressed by malignant cells of different lineages. This places CD6 as a potential target for novel therapies against haematological and non-haematological malignancies. Recent experimental evidence for the role of CD6 in cancer immunotherapies is summarised in this review, dealing with diverse and innovative strategies from the classical use of monoclonal antibodies to soluble recombinant decoys or the adoptive transfer of immune cells engineered with chimeric antigen receptors.

Keywords: CD166/ALCAM; CD318/CDCP1; CD44; CD6; adoptive cell transfer; cancer; chimeric antigen receptor; decoy receptor; immunotherapy; monoclonal antibodies; scavenger receptors.

Publication types

  • Review

MeSH terms

  • Activated-Leukocyte Cell Adhesion Molecule
  • Antigens, CD*
  • Antigens, Differentiation, T-Lymphocyte*
  • Immunotherapy
  • Neoplasms* / therapy
  • T-Lymphocytes

Substances

  • Activated-Leukocyte Cell Adhesion Molecule
  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD6 antigen

Grants and funding

Work is supported by projects PID2022-140932OB-I00 (funded by MCIN-AEI-10.13039-501100011033-FEDER, UE) and 2021-SGR-0113 (funded by AGAUR) to F.L. L.A.-S., L.C.-S. and V.P.-R., who are recipients of fellowships PREP2022-000394, PRE2020-093993 and FPU21-06217, respectively.