PD-L1, PD-1 Expression Differences Highlighted in NSCLC

Expression of PD-L1 and PD-1 on NSCLC cells and tumour infiltrating lymphocytes shows significant variation

medwireNews: German scientists have identified significant variation in both the expression of PD-L1 in patients with non-small-cell lung cancer (NSCLC), as well as expression of PD-L1 and PD-1 in tumour infiltrating lymphocytes (TILs).

PD-L1 and its receptor PD-1 were measured in NSCLC tissue specimens taken from 484 patients between 1993 and 2008, all of whom were naive to treatment targeting these proteins, the team reported last week at the 2015 European Lung Cancer Conference held in Geneva, Switzerland.

Immunohistochemistry revealed that PD-L1 expression was significantly higher in sarcomatoid tumours than other NSCLC types. Expression was also significantly higher in squamous cell carcinoma specimens than adenocarcinomas, affecting 31% and 22%, respectively.

There was also a positive correlation between histological tumour grade and PD-L1 expression that, on further analysis, was found to be significant only for patients with adenocarcinomas, report lead author Frido Brühl, from University Medical Center Freiburg, and co-workers.

The team also analysed PD-L1 and PD-1 expression on TILs and found three distinct patterns of expression – as well as expression of PD-1 alone, TILs were also found expressing only PD-L1 or both PD-L1 plus PD-1.

TILs positive for PD-L1 or PD-L1 plus PD-1 were found to be significantly associated with general lymphocytic infiltration, whereas those expressing only PD-1 were significantly associated with lymphocytes located in the stroma.

Moreover, the team found a significant and positive correlation between TIL number and membranous expression of PD-L1 on tumour cells. And PD-L1-positive TILs were associated with tumour cell expression of PD-L1, with the strongest correlation found for intraepithelial expression.

By contrast, the researchers did not find a correlation between PD-1 expression and TIL number.

“We therefore suggest an autocrine/paracrine loop between NSCLC cells and TILs to be responsible for PD-L1 expression on either cell and thus giving rise to possible escape from anti-tumor inflammatory responses”, the researchers say.

Frido Brühl explained to medwireNews that an efficient T-cell cytokine response with interleukin-10 and interferon-γ is already known to lead to expression of PD-L1 in different cell types including tumour cells.

“This might help understand PD-L1 negative tumors that still respond to anti-PD1 treatment which happens in about 10% of cases”, he said.

“Another conclusion could be to use anti-PD1 treatment first to enhance the immune response by ‘unleashing’ its potential and then follow up with an anti-PD-L1 therapy to counter possible adaption of the tumor by PD-L1 expression”, added Frido Brühl. “This is especially interesting since a concurrent double therapy could potentially lead to strong adverse effects.”

Recommending further research into expression of PD-1 on TILs and the interaction between PD-L1 expression and treatment response, he concluded: “The most pressing issue is certainly the introduction of common antibodies and standardized procedure for all future evaluations since right now each group is using different manufacturers, species, clones and arbitrary cut-off points.”

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