Immunotherapy, PD-L1 and the Pathologist
Immunotherapy consistently makes headlines as an effective tool in cancer treatment. What is it and why are pathologists so important in selecting patients most likely to benefit from this game changing therapy?
What is Immunotherapy
Cancer cells utilize PD-L1 to inactivate T cells and “cloak” themselves to the immune system. By blocking PD-L1 with antibodies, the tumor can be “unmasked” and the immune system unleased to attack the tumor.
Pathologists are crucial
Pathologists are integral to establishing PD-L1 status of tumors. By examining tumor cells for expression of PD-L1 through antibody tagged stains, pathologists can score the tumor. Often this is done in concert with stains for T cells to assess the inflammatory cell component around the tumor.
There are different immunohistochemical assays associated with each of the approved therapies. Based on the assay, therapy and indication, the threshold for positivity of PD-L1 varies. For some indications, PD-L1 is assessed only on tumor cells, while for other indications tumor cells and immune cells are assessed. It is likely that for at least some future indications, PD-L1 expression may only be assessed in immune cells. There is reasonably good correlation between the various IHC assays but the SP142 assay uses an amplified detection system that significantly increases detection in immune cells.
Issues with manual scoring
With any manual scoring system, there are innate problems with precision and accuracy. Results may not be reproducible from one pathologist to another, or even the same pathologist from day to day. One reliable way to circumvent this issue is with the use of image analysis.
To investigate the robustness of computer aided image analysis, Dr. Lija Joseph of Lowell General Hospital partnered with Applied Spectral Imaging to assess the analysis of PD-L1 in tumor tissue using the HiPath Pro system. The full paper can be found here.
The following image shows how important image analysis is assessing a true PD-L1 score in tumor tissue.
They found the HiPath Pro to be a robust system to evaluate PD-L1 IHC staining. Contrary to manual scoring that stops after a certain number of cells, HiPath Pro analysis includes every tumor cell, thus providing a statistically-based, reliable result that reflects the overall expression of PD-L1 of a specific tissue sample. Moreover, standardization, which is based on using computer-aided analysis, would eliminate the variability of a manual count for different pathologists. Overall, HiPath Pro overcomes manual sampling errors and insufficient cell-count and can be reliably used to assess PD-L1 expression.