immunotherapy

A new study on programmed death ligand 1 (PD-L1) expression in Basal Cell Carcinomas (BCCs) has shown some association and has the potential to provide valuable information for treatment options in the future, including the prognosis of treatment with directed immunotherapy.

 

This study assessed PD-L1 expression in treated and untreated BCCs, the most common type of skin cancer. The cross-sectional was performed by the Department of Dermatology at Stanford University, California and published online in JAMA Dermatology.

Programmed death ligand 1 (PD-L1) is a protein expressed by immune cells, it is a member of a family of co-stimulatory receptors that act by sending inhibitory signals to T cells, thus stopping the complex immune response. PD-L1 plays a role in protecting normal cells from being killed off. It does this by binding to its receptor PD-1 to inhibit the immune response to inflammatory reactions. Many cancers have the ability to upregulate PD-L1 on to their cells and tumor infiltrating lymphocytes (TILs), which protects them from an immune response and lets them escape programmed death, thus allowing the cancer cells to multiply unchecked.

Some previous cancer studies have found a link between PD-L1 expression levels and response to cancer treatment in other cancers including non-small-cell lung and prostate cancer. In these other studies, it was shown that PD-L1 expression is independently associated with more aggressive cancers and worse outcomes.

The role of the PD-1 and PD-L1 pathway in BCC is not well known. This study is aimed at investigating whether there is an association that can provide information about tumor behaviour in BCC. This is the initial study on the PD-1 pathway in BCCs.

Researchers performed immunohistochemical staining on formalin-fixed BCCs and assessed the percentage of tumor cells and tumor-infiltrating cells (TILs) expressing  PD-L1, as well as the intensity of expression and how it related to treatment. A total of 138 BCCs from 62 patients were included in this cross-sectional study.  Patients were recruited from the one academic tertiary referral centre. 90% of tumor cells and 95% of TILs were positive for PD-L1 expression. The intensity of expression was greater in treated than untreated BCCs.

However, there were limitations of this study as disclosed by the authors.

  • The small sample size made it difficult to analyze PD-L1 expression in BCCs exposed to different treatment modalities compared with treatment-naive BCCs in a statistically significant manner.
  • The study also lacked in paired samples obtained from the same BCC before and after treatment. Thus they cannot comment on the direction of causality even though they did find PD-L1 expression associated with a number of treatment types.
  • This study cannot be generalized as the tissue samples were all obtained from advanced or high-risk BCCs from the same specialty nonmelanoma skin cancer clinic. The PD-L1 expression in this study may have been higher than if the BCCs were obtained from a general dermatology clinic, where lower risk samples are likely to have been included in the study. The authors stated that they cannot comment on the direction of causality since high expression levels may be a consequence of treatment exposure or may reflect an underlying aggressive behaviour of the BCC.

The authors of the study concluded that if the same is true for BCCs as has been found in PD-1 pathway studies in other cancers, then testing for the presence of PD-L1 could provide valuable information determining treatment options. Potentially it will provide information regarding the prognosis of treatment with directed immunotherapy using PD-L1 inhibitors to target PD-1 or its ligand PD-L1. This concept needs future clinical trials due to the complexity of the immune system, however, is a potentially promising treatment option for inoperable and metastatic BCCs in the future.

 

Written By: Suzann Beaupark



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