Immuno-Oncology Advances in Applied Cellular Analysis - 7

Advances in Applied Cellular Analysis * PD-L1 Mutations and Immunotherapy Resistance

Antibodies that target PD-L1 or its receptor
PD-1 have shown extraordinary therapeutic
effects for many cancer patients-even for
those who are terminally ill. Because the treatments using such antibodies are extremely
expensive, the Kyoto scientists were keen to
find a biomarker that could predict the effectiveness of these drugs for individual patients.
"We identified PD-L1 structural alterations affecting the 3' untranslated region of the PD-L1
gene in 27% of patients with adult T-cell
leukemia/lymphoma by analyzing nextgeneration sequencing data," noted senior
study author Seishi Ogawa, M.D., Ph.D.,
professor in the Department of Pathology
and Tumor Biology at Kyoto University.
Due to the success of their initial finding, the investigators searched for similar structural alterations

7

| GENengnews.com

in sequencing data from a total of 10,210 samples
deposited in the Cancer Genome Atlas.
"Through this analysis, we found that such
abnormalities were found in many common
cancer types, including malignant lymphoma, as
well as stomach and cervical cancers," Dr. Ogawa
remarked. "We also generated human and mouse
cells having a similar structural alteration using
the CRISPR-Cas9 genome editing system and
confirmed that these cells actually showed an
elevated expression of the PD-L1 protein and
were able to escape the immune attack."
"To test the importance of such structural
alteration as a genetic marker, a Phase II and
other institutions," Dr. Ogawa added. "Once we
confirm the significance of these genetic
alterations, it'll be a game-changer for
immunotherapy in cancer." n

http://www.GENengnews.com

Immuno-Oncology Advances in Applied Cellular Analysis

Table of Contents for the Digital Edition of Immuno-Oncology Advances in Applied Cellular Analysis