Deciphering the genetic evolution of T-cell resistance in melanoma

Abstract

T–cell-based immunotherapy of melanoma becomes ineffective when β2m-deficient tumor cells of a human leukocyte antigen (HLA) class I-negative phenotype grow out. We demonstrated that an early-acquired chromosomal deletion and subsequent inactivating gene mutation lead to β2m deficiency, suggesting that melanoma cells can genetically evolve to avoid being recognized by CD8⁺ T cells.

Keywords:

• β2m deficiency
• CD8⁺ T cells
• genetic alterations
• HLA class I loss
• melanoma

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.