PONE-D-21-26179Programme Death Ligand 1 Expressions as a Surrogate for Determining Immunotherapy in Cervical carcinoma PatientsPLOS ONE

Dear Dr. Omenai,

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Academic Editor

PLOS ONE

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Reviewer #1: Yes

Reviewer #2: Partly

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

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Reviewer #1: This is an interesting paper and a lot of work has been done. However, there are many points to be clarified and improved upon:

1. The use of the English language and grammar should be improved.

2. Mention in the abstract the number of cases stained and scored. Mention the way the scoring was performed. mention links with clinical parameters. Ad which PDL1 clone was used.

3. Give a clear representation of the literature on PDL1 expression in cervical cancer. There are papers missing. Moreover, there is conflicting data on relation with prognosis and relation with amplification of the PDL1 locus. Please, elaborate and give cite all literature on cervical cancer.

4. PD-L1 is only one of the immune evasion mechanisms. The way the abstract is written at the moment it seems like it is the only one. Please, get more nuance into the discussion of the results.

5. Do comment on the various clones targeting PDL1 used for IHC. Is the clone the authors used also used by others or how does it relate to the standard clones used. Please, give more information. It is a big problem and should be addressed in the discussion. Please, show representative cases of positive, weak and negative expression in the SCC and AC histologies.

6. Was there other clinical data available on this patient cohort? HPV type, metastatic status? It would be interesting to compare expression percentages and expression patterns to other clinical data and survival.

7. Can the authors say something about tumor infiltrating myeloid cells being positive for PDL1? Or were there cases with high PDL1 expression on cells in the stromal compartment?

8. It is known that patients with expression PDL1 can also be unresponsive to PD1/PDL1 checkpoint inhibition. Please, tone down the discussion and also add literature on PD1/PDL1 being not effective and PD1/PDL1 being a biomarker with limited value.

Reviewer #2: Thank you for submitting this very interesting manuscript. The manuscript is well written and highlights the importance of PD-L1 testing in advanced cervical cancers, in particular the different rates of positivity based on histopathological characteristics. I have one major comment - and this is with regards to measuring the PD-L1 score. TPS is currently only used for non-small cell lung cancers, whereas other sites utilise the CPS scoring system. Your research has calculated the TPS score for PD-L1, which is a major flaw, in my opinion; and I wonder if the results would differ if the CPS scoring system was applied instead. The paper will need to be rewritten after recalculating the PD-L1 scores based on the CPS scoring system. In addition, please indicate if PD-L1 22C3 testing was used or SP142 assay.

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Reviewer #1: No

Reviewer #2: No

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Programme Death Ligand 1 Expressions as a Surrogate for Determining Immunotherapy in Cervical carcinoma Patients

PONE-D-21-26179R1

Dear Dr. Omenai,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Afsheen Raza, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments: