Structural and Functional Thymic Biomarkers Are Involved in the Pathogenesis of Thymic Epithelial Tumors: An Overview
Round 1
Reviewer 1 Report
In the current article, " Structural and functional thymic biomarkers are involved in the pathogenesis of thymic epithelial tumors: an overview" the authors have tried to overview the role of thymic epithelial cells as biomarkers. However, I believe, this overview lacks depth and needs deeper discussion on problems the field is facing and current therapeutic interventions available. I also encourage authors to discuss the status of clinical trials and the pre-clinical studies for the treatment of thymoma and thymic epithelial carcinoma. Discuss target drugs and their mode of action.
Comments
Comment 1: Abstract needs to be revised. The structuring of sentences needs a lot of improvement.
Comment 2: Please pay attention to the construction of sentences and punctuation.
Comment 3: Need to correct grammatical errors throughout the manuscript.
Comment 4: Appropriate spacing after the paragraphs and figures.
Comment 5: please discuss current clinical trials and therapeutic interventions (clinical and pre-clinical)
Comment 6: In conclusion, the authors mention several techniques such as multi-omics and gene expression profiles in addition to immunohistochemistry however, in the main text I did not notice any references pointing to this.
Line 12: In the discovery of…
Line 12-22: Please pay attention to Construction of sentences
Line 25: Remove “newly”
Line 25-30: Need to be revised. Construction of sentences
Figure 1 legend: Main cellular compartments of thymus? Include lines 78-89 in the figure legend.
Line 98: Text size and font..
Table 1: Contents of table does not reflect the title? Please provide more valid information in the table. It is advisable to list the clinical significance of each gene mentioned in the review. There is enough literature available for each gene target and its involvement in pathogenesis of autoimmune diseases and cancer.
Line 129: led to “discovery”.. please correct elsewhere.
Line 128-135: Sentence construction.
Line 184-189: Grammatical errors.. Sentence construction (Throughout the manuscript)
Line 224: Please pay attention to the uniformity of font and text size
Author Response
Comments and Suggestions for Authors
In the current article, " Structural and functional thymic biomarkers are involved in the pathogenesis of thymic epithelial tumors: an overview" the authors have tried to overview the role of thymic epithelial cells as biomarkers. However, I believe, this overview lacks depth and needs deeper discussion on problems the field is facing and current therapeutic interventions available. I also encourage authors to discuss the status of clinical trials and the pre-clinical studies for the treatment of thymoma and thymic epithelial carcinoma. Discuss target drugs and their mode of action.
We thank very much the Reviewer for the observations. In effect, problems and relevant biomarkers in thymic epithelial cells are very numerous, and were extensively characterized by experimental approaches in the last years. Moreover, much work should still be done. It would be impossible to go into the depth in a single “overview”. According to your request, however, we added a paragraph on clinical trials and experimental and preclinical studies, involving target therapies. We could not add more than this: the review is very very long, and to go into the deep in the several topics would require a very extensive treatise. We would be glad, eventually, to consider in the future a new review going more in depth on the topic/topics you mention.
Comments
Comment 1: Abstract needs to be revised. The structuring of sentences needs a lot of improvement.
Response: done
Comment 2: Please pay attention to the construction of sentences and punctuation.
Response: done
Comment 3: Need to correct grammatical errors throughout the manuscript.
Response: done
Answers to comments 1-2-3: the English revision was performed by an English mother language specialist.
Comment 4: Appropriate spacing after the paragraphs and figures:
Response: done
Comment 5: please discuss current clinical trials and therapeutic interventions (clinical and pre-clinical):
Response: based on your request we added a complex and exhaustive paragraph on “Targeted therapies in TET: a short overview of current available experimental and clinical data and of perspectives advances”
Comment 6: In conclusion, the authors mention several techniques such as multi-omics and gene expression profiles in addition to immunohistochemistry however, in the main text I did not notice any references pointing to this.
Responce:The references in the original version mentioning the molecular studies were in effects few. In the revised ver. 1 we added several references and also a paragraph – on your request- focusing on multi-omics and molecular biological studies, adding the relevant references
Line 12: In the discovery of…
Response: we changed the phrase
Line 12-22: Please pay attention to Construction of sentences.
Response: done
Line 25: Remove “newly”.
Response: done
Line 25-30: Need to be revised. Construction of sentences.
Response: done
Figure 1 legend: Main cellular compartments of thymus? Include lines 78-89 in the figure legend.
Response: done.
Line 98: Text size and font..
Response: done
Table 1: Contents of table does not reflect the title? Please provide more valid information in the table. It is advisable to list the clinical significance of each gene mentioned in the review. There is enough literature available for each gene target and its involvement in pathogenesis of autoimmune diseases and cancer.
Response: the Table was revised and further informations added. New references have been added and cited in the Table as well as in the list of references. The title of the Table was slightly modified. Because the table in vertical became too long, we changed the Table in horizontal. The Pptx slide corresponding to Table 1 will be provided for better evaluation
Line 129: led to “discovery”.. please correct elsewhere.
Response: done
Line 128-135: Sentence construction.
Response: done
Line 184-189: Grammatical errors.. Sentence construction (Throughout the manuscript)
Response: done
Line 224: Please pay attention to the uniformity of font and text size
Response: done
Moreover, we would like to add that:
In particular the English language of the paper was reviewed by an English mother language expert.
Reviewer 2 Report
This review article entitled “Structural and functional thymic biomarkers are involved in the pathogenesis of thymic epithelial tumors: an overview [immuno-1679219]” reviewed the development of thymic cells and their function for maturation, and relation to abnormality, then, thymomas and their associated immunological complication. I think this review is a comprehensive and good review although more issues on thymoma will be needed (but there is a limitation for words count and too long to add them.)
- Thymus separate into parathyroid from third branchial clefts. CASLE in the neck will be similar pathogenesis.
- What do you think of the role of CD70 in TET? [optional]
- What do you think of the similarities to SCLC-P (Pou2fc expressing SCLC) with TETs? [optional]
Good luck the authors.
Author Response
Comments and Suggestions for Authors
This review article entitled “Structural and functional thymic biomarkers are involved in the pathogenesis of thymic epithelial tumors: an overview [immuno-1679219]” reviewed the development of thymic cells and their function for maturation, and relation to abnormality, then, thymomas and their associated immunological complication. I think this review is a comprehensive and good review although more issues on thymoma will be needed (but there is a limitation for words count and too long to add them.)
- Thymus separate into parathyroid from third branchial clefts. CASLE in the neck will be similar pathogenesis.
Response: Thanks for your observation. However, we cited a study (Liu et al, cit no. 19) mentioning that ” the pair of inferior parathyroid glands develop together with the thymus from the 3rd pharyngeal pouches, while the pair of superior parathyroid glands (not present in mice) develop with the ultimobranchial bodies from the 4th pharyngeal pouches”.
- What do you think of the role of CD70 in TET? [optional]
Response: Excuse us, we have no direct experience of this marker.
- What do you think of the similarities to SCLC-P (Pou2fc expressing SCLC) with TETs? [optional]
Response: We added a paragraph mentioning shortly the SCLC-P (POU2F3 expressing) and the experimental therapeutical work ongoing; our comment is that the knowledge are certainly much extensive in SCLC than in the thymus, but certainly this example will bring to a deeper study of this marker in TET
Moreover, we would like to add that:
In particular the English language of the paper was reviewed by an English mother language expert.
The Table 1, modified on request of one of the Reviewers, resulted too long and was changed in horizontal in order to contain more informations. The Pptx slide corresponding to Table 1 will be provided for better evaluation
Moreover, based on the request of one of the Reviewers we added a complex and exhaustive paragraph on “Targeted therapies in TET: a short overview of current available experimental and clinical data and of perspectives advances”
Good luck the authors.
Thanks for the whishes
Reviewer 3 Report
The article is consistent within itself. The references are relevant and recent. The cited sources are referenced correctly. Appropriate and key studies are included. The paper is comprehensive, the flow is logical and the data is presented critically.
However, there are some specific comments on weaknesses of the article and what could be improved:
Specific comments on weaknesses of the article and what could be improved:
Major points - none
Minor points
- Text of the figure 1 should be placed in the text of the figure, not in the manuscript text
- The same goes for the other figures captions
- Some of the text is in bigger font size, is it necessary?
Author Response
Comments and Suggestions for Authors
The article is consistent within itself. The references are relevant and recent. The cited sources are referenced correctly. Appropriate and key studies are included. The paper is comprehensive, the flow is logical and the data is presented critically.
However, there are some specific comments on weaknesses of the article and what could be improved:
Specific comments on weaknesses of the article and what could be improved:
Major points - none
Minor points
Response: Thanks for your positive comments to the article. We really did a big effort and we tried to provide relevant and updated references
- Text of the figure 1 should be placed in the text of the figure, not in the manuscript text
Response: we changed the position of the Figure legend.
- The same goes for the other figures captions:
Response: we changed the position of the Figure legends and of the Table 1 and relative abbreviations
- Some of the text is in bigger font size, is it necessary?
Response: These editing problems were solved.
Moreover, we would like to add that:
In particular the English language of the paper was reviewed by an English mother language expert.
The Table 1, modified on request of one of the Reviewers, resulted too long and was changed in horizontal in order to contain more informations. The Pptx slide corresponding to Table 1 will be provided for better evaluation
Moreover, based on the request of one of the Reviewers we added a complex and exhaustive paragraph on “Targeted therapies in TET: a short overview of current available experimental and clinical data and of perspectives advances”
Round 2
Reviewer 1 Report
The authors addressed most of the comments and added a section on targeted therapies in TET. I am satisfied with the changes and the current review article can be accepted in its current form after careful editing and formatting is completed that fit the journal's requirements.
