AI Article Synopsis

  • The study investigates the role of MICA/B proteins in intrahepatic cholangiocarcinoma (iCCA), a type of liver cancer that presents late and has a poor prognosis.
  • Elevated levels of MICA/B were found in iCCA patients, linked to cellular stress, promoting cancer escape from immune recognition.
  • Using a specific antibody (7C6), researchers demonstrated that it enhances the ability of natural killer (NK) cells to attack cancer cells, suggesting its potential as an immunotherapy for iCCA.

Article Abstract

The major histocompatibility complex-class I chain related proteins A and B (MICA/B) is upregulated because of cellular stress and MICA/B shedding by cancer cells causes escape from NKG2D recognition favoring the emergence of cancers. Cholangiocarcinoma (CCA) is a relatively rare, though increasingly prevalent, primary liver cancer characterized by a late clinical presentation and a dismal prognosis. We explored the NKG2D-MICA/B axis in NK cells from 41 patients with intrahepatic cholangiocarcinoma (iCCA). The MICA/B-specific 7C6 mAb was used for antibody-dependent cytotoxicity (ADCC) experiments using circulating, non tumor liver- and tumor-infiltrating NK cells against the HuCCT-1 cell line and patient-derived primary iCCA cells as targets. MICA/B were more expressed in iCCA than in non-tumoral tissue, MICA transcription being higher in moderately-differentiated compared with poorly-differentiated cancer. Serum MICA was elevated in iCCA patients in line with higher expression of ADAM10 and ADAM17 that are responsible for proteolytic release of MICA/B from tumor. Addition of 7C6 significantly boosted peripheral, liver- and tumor-infiltrating-NK cell degranulation and IFNγ production toward MICA/B-expressing established cell lines and autologous iCCA patient target cells. Our data show that anti-MICA/B drives NK cell anti-tumor activity, and provide preclinical evidence in support of 7C6 as a potential immunotherapeutic tool for iCCA.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8865231PMC
http://dx.doi.org/10.1080/2162402X.2022.2035919DOI Listing

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