Role of Tumor-Infiltrating Lymphocytes and the Tumor Microenvironment in the Survival of Malignant Parotid Gland Tumors: A Two-Centre Retrospective Analysis of 107 Patients

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The manuscript provides insights into the role of TILs in the survival of malignant parotid gland tumors.

I could not access and evaluate any figures.

Ensure the manuscript consistently states whether TILs are associated with good or adverse prognosis and provide mechanisms and study findings. Provide a clear hypothesis about the role of TILs (adverse or good prognosis). Expand on the background of TILs in the context of tumor microenvironment and prognosis.

Redesign tables for clarity and professionalism. Include abbreviations under each table.

Include figures for correlation analyses to visually represent the data.

Re-evaluate the correlation analyses to ensure accuracy. For instance, if high TILs correlate with low T, ensure both show a negative correlation instead of positive.

Discuss the mechanisms by which TILs influence prognosis regarding the study findings and existing literature.

 

Report the correlation analysis among pathologists to demonstrate the consistency of TIL evaluations.

Comments on the Quality of English Language

Moderate editing of English language required

Author Response

Dear Reviewers,

Thanks for reviewing our manuscript and for the valuable comments that helped us clarify some relevant aspects that were missed or unclear in the first version of the paper. 

We have read carefully your comments and made the changes to address comments and concerns using track-changes.

Our answers to your concerns are blue bolded. The paper has been entirely revised to reduce plagiarism and to improve the English quality and readability. 

We hope that the changes made in the revised manuscript and responses provided below have adequately addressed the reviewer’s comments and made this paper stronger.

 

Review 1

The manuscript provides insights into the role of TILs in the survival of malignant parotid gland tumors.

1. I could not access and evaluate any figures. 

We hope that now the figures are fully accessible.

2. Ensure the manuscript consistently states whether TILs are associated with good or adverse prognosis and provide mechanisms and study findings. Provide a clear hypothesis about the role of TILs (adverse or good prognosis). Expand on the background of TILs in the context of tumor microenvironment and prognosis.

Thanks for your comment. We discussed this point and we also added info about the      high/low TILs and their role in the result sections and in the discussion. 

3. Redesign tables for clarity and professionalism. Include abbreviations under each table.

Thanks for your comment. We redesigned the tables and included abbreviations.

4. Include figures for correlation analyses to visually represent the data.

We included figures 1, 2 and 3 that shows the results of multilinear regression analyses. 

5. Re-evaluate the correlation analyses to ensure accuracy. For instance, if high TILs correlate with low T, ensure both show a negative correlation instead of positive.

We performed additional multinear regression analyses and we fully described in the material and method section (statistical analyses) which were “x” and “y” parameters. We also clarified the statistic; in particular we only used Pearson. In the results are now reported the “R” value in addition to p for clarity. We also clarified in the results the meaning of “negative” or “positive” correlation with a sentence in addition to the statistic values. 

Reviewer 2 Report

Comments and Suggestions for Authors

1.        Lines 120-121. “Spearman (S) and Pearson (P) tests were used to correlate TILs with grading, with tumor, with metastasis, with survival and treatment used.” Why did the authors use these tests for survival? Usually survival analyses, as time-to-event data, are specifically analyzed with log-rank test or multivariate models.

2.        Survival. When survival is mentioned, is it overall survival or disease-free survival? It may be useful to specify it.

3.        Where TILs have been counted? Only in the stroma, as in breast carcinoma? Or inside the tumor? It is explained in the Discussion, but a little explanation could also be provided in the M&M section.

4.        Lines 174-191. P is the statistical p or is it Pearson coefficient? When there is a positive/negative correlation, a numeric value of this correlation (not only its statistical significance) could be added.

5.        Why is it necessary to underline that all lesions were biopsy-proved in surgical specimens? Sometimes malignancies are discovered directly in surgical specimens. Would the authors probably underline that all lesions were histologically confirmed in surgical specimens?

Author Response

Dear Reviewers,

Thanks for reviewing our manuscript and for the valuable comments that helped us clarify some relevant aspects that were missed or unclear in the first version of the paper. 

We have read carefully your comments and made the changes to address comments and concerns using track-changes.

Our answers to your concerns are blue bolded. The paper has been entirely revised to reduce plagiarism and to improve the English quality and readability. 

We hope that the changes made in the revised manuscript and responses provided below have adequately addressed the reviewer’s comments and made this paper stronger.

1. Lines 120-121. “Spearman (S) and Pearson (P) tests were used to correlate TILs with grading, with tumor, with metastasis, with survival and treatment used.” Why did the authors use these tests for survival? Usually survival analyses, as time-to-event data, are specifically analyzed with log-rank test or multivariate models.

Thank you for this comment. We performed multilinear regression analyses. Details about the method have been described in the material and methods (statistical analyses) and we also added three figures to visually show the results of the analyses. 

2. Survival. When survival is mentioned, is it overall survival or disease-free survival? It may be useful to specify it.

Thanks for your comment. We have corrected it (OS).

3. Where TILs have been counted? Only in the stroma, as in breast carcinoma? Or inside the tumor? It is explained in the Discussion, but a little explanation could also be provided in the M&M section.

Thanks for your comment; we added the information in the methods section.

4. Lines 174-191. P is the statistical p or is it Pearson coefficient? When there is a positive/negative correlation, a numeric value of this correlation (not only its statistical significance) could be added.

We added “R” value in addition to p. Thank you for this note.

5.        Why is it necessary to underline that all lesions were biopsy-proved in surgical specimens? Sometimes malignancies are discovered directly in surgical specimens. Would the authors probably underline that all lesions were histologically confirmed in surgical specimens?

Thanks for your comment; we corrected it.

Reviewer 3 Report

Comments and Suggestions for Authors

hello

thank you for the paper, its quite interesting

title =ok

abstract- explain TIL in the beginning of the abstract 

abstract is structured and well presented

abstract ok

key words -ok

introduction:

introduction is short and well written

please add the list of most common parotid gland cancers in the introduction + references

please add in the introduction why diagnostics and treatment of parotid cancers is troublesome, and how potential TIL can help or improve future studies

material and methods section

good written -ok

material and methods are sound, well descried

please highlight the inclusion criteria for the study

what was the histopathological protocol consisted of? please explain

statistics are ok

results =OK

results need more clarification, how could they improve the parotid gland cancers outcomes and diagnostics

table 1 is too big and not descriptive, missing abbreviations legends - please improve

also a figure, a flow-chart of the included/excluded patients for the study should be added, and described why did it happen 

surgical results are short

chapter 3.3 is well written, nothing to add more

table 2- missing abbreviations, table is too big and not descriptive enough

at the end of the result please highlight the most important results and their possible usage for future studies

discussion - is well written and sound

discussion is short, please improve it and add more TIL suggested role in parotid cancer

rest OK

study limitations are well presented

conclusions are sound

study references are suitable

rest is quite alright

please improve the paper for any future considerations 

 

Author Response

hello, thank you for the paper, its quite interesting

title =ok

abstract- explain TIL in the beginning of the abstract

Thanks for your comment, we have corrected it.

abstract is structured and well presented. abstract ok. key words -ok

introduction:

introduction is short and well written

please add the list of most common parotid gland cancers in the introduction + references

Thanks for your comment, we added in the introduction the most common parotid malignancies.

please add in the introduction why diagnostics and treatment of parotid cancers is troublesome, and how potential TIL can help or improve future studies

Thanks for your comment, we added an explanation.

material and methods section

good written -ok

material and methods are sound, well descried

please highlight the inclusion criteria for the study

Thanks for your comment, we have included the section “inclusion criteria”.

what was the histopathological protocol consisted of?

The histopathological analysis of TILs is already explained in the methods section.

statistics are ok

results =OK

results need more clarification, how could they improve the parotid gland cancers outcomes and diagnostics

Thanks for your comment, we improved the “results” section and the statistical analysis.

table 1 is too big and not descriptive, missing abbreviations legends - please improve

also a figure, a flow-chart of the included/excluded patients for the study should be added, and described why did it happen 

Thanks for these two comments. We reduced the table 1 and we added the abbreviations.

surgical results are short

Thanks for your comment; we have entered the additional operating data that we have available, i.e. the operating time.

chapter 3.3 is well written, nothing to add more

table 2- missing abbreviations, table is too big and not descriptive enough

Thank for your comment. We reduced the table’s dimensions.

at the end of the result please highlight the most important results and their possible usage for future studies

Thanks for your comment, we have added it.

discussion - is well written and sound

discussion is short, please improve it and add more TIL suggested role in parotid cancer

Thanks for your comment, we improved the discussion section.

rest OK

study limitations are well presented

conclusions are sound

study references are suitable

rest is quite alright

please improve the paper for any future considerations 

 

 

 

We really appreciated your careful and thoughtful evaluation of our manuscript and hope that this revised version meets with your approval. We have tracked all changes using colored words in the revised manuscript. Thanks again for your interest in our work. We await your review of our revised manuscript.

 

Sincerely yours,

The Authors

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

The authors have addressed all my concerns

Reviewer 3 Report

Comments and Suggestions for Authors

hello

thank you for your valuable comments

with kind regards