IL-2/IL-2R signaling and IL-2Rα-targeted therapy in anaplastic large cell lymphoma

Pathologie (Heidelb). 2022 Aug;43(Suppl 1):25-30. doi: 10.1007/s00292-022-01108-x. Epub 2022 Sep 12.

Abstract

Anaplastic large cell lymphoma (ALCL) is a CD30-positive non-Hodgkin's T‑cell lymphoma. Despite the implementation of CD30 antibody-drug conjugate-targeted therapy into front-line treatment regimens, the prognosis of some subtypes of the disease remains unsatisfactory. In the relapsed/refractory setting, effective second-line treatment options are still lacking. However, it has been reported that blockade of direct downstream targets of activator protein‑1 (AP-1) transcription factors, which are highly dysregulated in ALCL, results in complete and sustained remission in late-stage relapsed/refractory anaplastic lymphoma kinase (ALK)-positive ALCL patients. Moreover, it has been identified that involvement of the BATF3/AP‑1 module promotes lymphomagenesis via oncogenic BATF3/IL-2/IL-2R signaling through hyperphosphorylation of ERK1/2, STAT1, and STAT5 in ALCL cells regardless of their ALK status. Therefore, targeting BATF3/IL-2/IL-2R signaling may represent a novel therapeutic alternative for ALCL patients.

Keywords: Activator protein‑1; Anaplastic large cell lymphoma; BATF3 transcription factor; Interleukin‑2 receptor α; Super-enhancer.

MeSH terms

  • Anaplastic Lymphoma Kinase / therapeutic use
  • Humans
  • Interleukin-2 / therapeutic use
  • Interleukin-2 Receptor alpha Subunit / therapeutic use
  • Lymphoma, Large-Cell, Anaplastic* / drug therapy
  • Receptor Protein-Tyrosine Kinases / therapeutic use
  • Transcription Factor AP-1 / therapeutic use

Substances

  • Interleukin-2
  • Receptor Protein-Tyrosine Kinases
  • Anaplastic Lymphoma Kinase
  • Transcription Factor AP-1
  • Interleukin-2 Receptor alpha Subunit