Immunohistochemical Expression of Programmed Cell Death Ligand 1 (PD-L1) in Human Cutaneous Malignant Melanoma: A Narrative Review with Historical Perspectives
, Teresa Lettini 1,†, Anna Colagrande 1, Irma Trilli 2, Francesca Ambrogio 3, Carmelo Laface 4, Paola Parente 5, Eugenio Maiorano 1 and Giuseppe Ingravallo 1
Round 1
Reviewer 1 Report
There are some minor comments.
- It would be better to add the major diagnostic criteria for mcEDS-CHST14 and which genetic tests were used to confirm the diagnosis.
- It would be better to add if other otological features were present.
- Please replace all photos of Fig. 1 with larger, explicit photos.
Please check English grammar.
Author Response
Thank you very much.
We have corrected all fields with you precious suggestions.
Thanks again.
Reviewer 2 Report
In this manuscript, Cazzato and Lettini et al. provided a detailed review of immunohistochemistry expression of PD-L1 as an important biomarker for diagnostic and treatment decision making in the clinics. The authors summarised several published studies that described the advantages and disadvantages of using PD-L1 immunoexpression to guide clinicians for selecting the optimal treatment options for patients. Although PD-L1 is still a diagnostic assay to be used in the clinics, several issues including Intra- and Inter-heterogeneity of PD-L1 expression, tumour microenvironment, and pattern of TIL distribution were further described in the manuscript. The manuscript is clear, however, there are certain sections to be removed or improved.
Specific comments:
1. Remove Section 2 Materials and Methods. The heading layout of a review paper generally does not include materials and methods.
2. Section 4 is missing. Can the authors clarify?
3. Since PD-L1 may not be a reliable assay, will adding/integrating other data sets including gene expression signatures, TMB (tumour mutation burden), single-cell sequencing expression will provide a better diagnostic values. For example, will patients with high PD-L1 immunoexpression (based on IHC) and high TMB (based on DNA sequencing) a better predictive signature in response to treatment (immunotherapy)? Can the authors discuss and include this in the review paper? This should be a section by itself.
Minor editing of English language required.
Author Response
Reviewer n'1: In this manuscript, Cazzato and Lettini et al. provided a detailed review of immunohistochemistry expression of PD-L1 as an important biomarker for diagnostic and treatment decision making in the clinics. The authors summarised several published studies that described the advantages and disadvantages of using PD-L1 immunoexpression to guide clinicians for selecting the optimal treatment options for patients. Although PD-L1 is still a diagnostic assay to be used in the clinics, several issues including Intra- and Inter-heterogeneity of PD-L1 expression, tumour microenvironment, and pattern of TIL distribution were further described in the manuscript. The manuscript is clear, however, there are certain sections to be removed or improved.
Answer n'1: Dear Reviewer n'2, thank you very much for your useful and kind tips. We have corrected all following your suggestions.
Reviewer n'2: 1. Remove Section 2 Materials and Methods. The heading layout of a review paper generally does not include materials and methods.
Answer n'2: Dear Reviewer n'2, ok. We have removed the Material and methods section. Thank you.
Reviewer n'2: 2. Section 4 is missing. Can the authors clarify?
Answer n'3: Dear Reviewer n'2, thank you very much. There was a mistake with the correct number of the paragraph. We have corrected it.
Reviewer n'2: 3. Since PD-L1 may not be a reliable assay, will adding/integrating other data sets including gene expression signatures, TMB (tumour mutation burden), single-cell sequencing expression will provide a better diagnostic values. For example, will patients with high PD-L1 immunoexpression (based on IHC) and high TMB (based on DNA sequencing) a better predictive signature in response to treatment (immunotherapy)? Can the authors discuss and include this in the review paper? This should be a section by itself.
Answer n'3: Dear Reviewer n'2, thank you. This is a great suggestion/idea. So, we have added a paragraph about this topic with other important papers that are related to it. A warm greeting and thanks again.
