What is the role of HMGB1 in immunotherapeutic targeting in pediatric oncology?

Updated: Mar 20, 2018
  • Author: Crystal L Mackall, MD; Chief Editor: Jennifer Reikes Willert, MD  more...
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The release of inflammatory mediators (alarmins) as tumors die off can lead to immune responses against self-molecules. HMGB1 is one such nuclear protein that binds the receptor for advanced glycation end products (RAGE) TLR2 or TLR4. [21, 22] Tumor cells that undergo apoptosis in vitro in response to anthracyclines can be picked up by DCs through TLR4 and lead to long-term tumor protection without addition of adjuvants.

The relevance of this in pediatric oncology has been demonstrated in rhabdomyosarcomas, in which preclinical data have shown that HMGB1 stimulates myogenesis through RAGE; this tumor may reduce expression of RAGE as a means of survival. [23] The implications are that alarmins are a byproduct of tumor cell death, are purposefully underexpressed by tumors to avoid detection by the immune system, and are a potential novel target for immunotherapy.

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