Chasing Uterine Cancer with NK Cell-Based Immunotherapies

Round 1

Reviewer 1 Report

The manuscript of Vijay Kumar, Caitlin Bauer and John H. Stewart IV is dedicated to a literature review on recent data on application of NK cell-targeted anticancer therapy, in particular for immunotherapy of uterine cancer. This field of investigation is significant because uterine cancer is surely an important biomedical problem and clarification of poorly understood mechanisms of the disease related to NK cells is of importance for development of novel effective therapeutic approaches to treat these diseases. The significance of this review is considerable, since the presented summary of literature data and their analysis give an objective integral picture of existing ideas on the indicated topic and highlight possible ways of practical use of the accumulated knowledge. These include information concerning the role of NK cells in maintaining immune homeostasis, description of the features and differences of uterine NK cells from NK cells in peripheral blood, discussing the functions of NK cells in the uterine cancer immune microenvironment. An important aspect of the work is the discussion of the NK cell-based therapies in different cancers and future perspective of NK cell-based immunotherapy for uterine cancer.

In general the review is well presented; the data are of considerable novelty and interest. I have no suggestion to improve the quality of the manuscript.

Author Response

We highly appreciate the reviewer for such a positive feedback.

Reviewer 2 Report

 

This review manuscript prepared by Kumar et al. is devoted to NK cell role in uterine cancer. It contains six parts including introduction, future perspective consideration and conclusion. In the main parts, the authors give general information about NK cell phenotypes and functions, describe uterine NK cells and their behavior in immune microenvironment and discuss the possibilities of NK cell-based cancer therapies. The work is quite good. The information collected in the manuscript is well structured. However, some parts look too long and could be shortened.  The manuscript is beautifully illustrated. The language is good. I recommend this manuscript for publication in Future Pharmacology after certain revision.

  

 

Recommendations:

 

 

1)   It would be desirable to add more detailed information about chemokine receptors in NK cells expressed in uterine and uterine cancer and describe the differences from circulating NK cells.

2)   The statement “NK cell loss may be attributed to decreased HLA-E expression, as HLA-E is usually upregulated in response to cancer progression” should be expanded for better understanding.

3)   The Lin−IL-7Rα−CD56dimCD16+  circulated NK cell subset should still be listed as mature, not immature (line 96).

4)   Table 1: ILT2 is another name of LILRB1 inhibitory receptor (CD85j); it should be listed twice.

5)   Some abbreviations are redundant since they are used ones in the text (for example, NKD). On the other hand, other abbreviations are not deciphered in the text (for example, EC). It should be corrected.

6)   All the text should be thoroughly checked to correct misprints (examples: line 95 – ‘l’ should be superlinear; line 98 – T , B cells should be typed without hyphen).

Author Response

We are thankful to the reviewer for providing the recommendations to update the article for resubmission. Kindly find below our pointwise answers to your queries:

  Recommendations:

• It would be desirable to add more detailed information about chemokine receptors in NK cells expressed in uterine and uterine cancer and describe the differences from circulating NK cells.

Ans. We have updated the required information in the article and all the changes are highlighted as red in the updated version.

• The statement “NK cell loss may be attributed to decreased HLA-E expression, as HLA-E is usually upregulated in response to cancer progression” should be expanded for better understanding.

Ans. We have discussed the information in detail as suggested. Updates are highlighted in red.

• The Lin−IL-7Rα−CD56dimCD16+  circulated NK cell subset should still be listed as mature, not immature (line 96).

Ans. We have corrected as suggested and it is highlighted in red in the updated article.

4)   Table 1: ILT2 is another name of LILRB1 inhibitory receptor (CD85j); it should be listed twice.

Ans. We have corrected in the updated table.

• Some abbreviations are redundant since they are used ones in the text (for example, NKD). On the other hand, other abbreviations are not deciphered in the text (for example, EC). It should be corrected.

Ans. We have deleted the abbreviation, NKD along with others as suggested. However, we have kept some in the text as they are standard and are helpful to readers. We have explained EC at place used for the first time in the text.

• All the text should be thoroughly checked to correct misprints (examples: line 95 – ‘l’ should be superlinear; line 98 – T , B cells should be typed without hyphen).

Ans. We have corrected these typo mistakes in the updated article.

Reviewer 3 Report

The authors Vijay Kumar et al wrote a systematic review on “Chasing uterine cancer with NK cell-based Immunotherapies” The authors updated the current knowledge on the uterine immune microenvironment and NK cell-targeted uterine cancer therapeutics. The subject is novel and well-written. I suggest authors address the following comments.

Major Comments

1.     I suggest authors make a table for future perspectives and a conclusion section by highlighting the key findings about natural killer cells and their role in uterine cancer.

2.     There are grammatical, spelling, and spacing errors in the manuscript, I suggest authors correct them wherever applicable.

 

 

Author Response

We appreciate the reviewer for positive comments. Below are our answers to the comments:

1. I suggest authors make a table for future perspectives and a conclusion section by highlighting the key findings about natural killer cells and their role in uterine cancer.

Ans. As suggested we have added a table (Table 2).

2. There are grammatical, spelling, and spacing errors in the manuscript, I suggest authors correct them wherever applicable.

Ans. We have checked and corrected suggested errors in the updated version of the article.