TLR2

Overview

TLR2 encodes Toll-Like Receptor 2, a pattern-recognition receptor of the innate immune system that activates NF-kB signaling upon microbial ligand binding. In mantle cell lymphoma (MCL), gain-of-function TLR2 mutations are enriched in the SOX11-negative/IGHV-mutated indolent subtype, where they elevate IL-6 and IL-1RA secretion, suggesting a role for microenvironment cytokine signaling in this distinct biological subset.

Alterations observed in the corpus

  • Gain-of-function mutations p.D327V and p.Y298S detected in 2/171 SOX11-negative/IGHV-mutated MCL cases; the p.D327V allele has also been reported in IGHV-mutated CLL; functional studies show elevated IL-1RA and IL-6 secretion from cells carrying these alleles PMID:24145436.

Cancer types (linked)

  • MCL: TLR2 mutations define part of the SOX11-negative/IGHV-mutated indolent MCL subset; the gain-of-function phenotype implicates the microenvironment cytokine axis (IL-6/IL-1RA) in this low-CNA, indolent biology PMID:24145436.

Co-occurrence and mutual exclusivity

  • TLR2 mutations co-occur with CCND1 exon-1 mutations in the SOX11-negative/IGHV-mutated indolent MCL subtype; this contrasts with the SOX11-positive/IGHV-unmutated aggressive MCL subset defined by ATM, NSD2, KMT2D, and MEF2B mutations PMID:24145436.

Therapeutic relevance

  • Gain-of-function TLR2 alleles increase IL-6 secretion, supporting microenvironment cytokine signaling (particularly IL-6) as a candidate therapeutic axis in SOX11-negative MCL PMID:24145436.

Open questions

  • Mechanism by which TLR2 gain-of-function alleles are selected in the IGHV-mutated germinal-center microenvironment of indolent MCL is unresolved PMID:24145436.
  • Whether the same TLR2 alleles observed in CLL and MCL confer convergent IL-6/IL-1RA phenotypes in both contexts has not been functionally validated PMID:24145436.

Sources

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