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PMLBCL : Escape from Immuno-surveillance

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Escape from Immunosurveillance: The tumor microenvironment in primary mediastinal large B-cell lymphomas (PMLBCL) causes dysregulated immune response which allows the tumor cells to escape immunosurveillance.

Expression of major histocompatibility complex (MHC) genes and proteins is regulated by MHC class II transactivator CIITA at 16p13.13 locus. Rearrangements or mutations in CIITA gene with downregulation of MHC class II proteins have been found in approximately 53% of PMLBCL.

Translocations involving CIITA also impact PDL1 and PDL2 resulting in their overexpression. About 63% of PMLBCL show amplification of 9p24.1 containing PDL1 and PDL2 further causing their amplification. PDL1 and PDL2 interact with PD1 on T-lymphocytes and cause T-cell anergy (functional inactivation following encounter with antigen). This allows tumor cells to evade immunosurveillance. The combination of CIITA alterations and amplification of the PDL locus is unique to PMLBCL among large B-cell lymphomas but is also seen in classic Hodgkin lymphoma.

Image source: Lees, Charlotte & Keane, Colm & Gunawardana, Jay. (2019). Biology and therapy of primary mediastinal B‐cell lymphoma: current status and future directions. British Journal of Haematology. 185. 10.1111/bjh.15778; used under Creative Commons Attribution-noncommercial 4.0 International License.

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