Direct CD32 T-cell cytotoxicity: implications for breast cancer prognosis and treatment

CD32-chimeric receptor T cell identifies CD32 cell surface ligand(s), on breast cancer (BC) cells, leading to BC cell elimination in vitro and in vivo and allowing detection of genes prognostically relevant.

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Thank you for this interesting contribution to Life Science Alliance. We are looking forward to receiving your revised manuscript. --An editable version of the final text (.DOC or .DOCX) is needed for copyediting (no PDFs).
--High-resolution figure, supplementary figure and video files uploaded as individual files: See our detailed guidelines for preparing your production-ready images, https://www.life-science-alliance.org/authors --Summary blurb (enter in submission system): A short text summarizing in a single sentence the study (max. 200 characters including spaces). This text is used in conjunction with the titles of papers, hence should be informative and complementary to the title and running title. It should describe the context and significance of the findings for a general readership; it should be written in the present tense and refer to the work in the third person. Author names should not be mentioned.
--By submitting a revision, you attest that you are aware of our payment policies found here: https://www.life-sciencealliance.org/copyright-license-fee B. MANUSCRIPT ORGANIZATION AND FORMATTING: Full guidelines are available on our Instructions for Authors page, https://www.life-science-alliance.org/authors We encourage our authors to provide original source data, particularly uncropped/-processed electrophoretic blots and spreadsheets for the main figures of the manuscript. If you would like to add source data, we would welcome one PDF/Excel-file per figure for this information. These files will be linked online as supplementary "Source Data" files. ***IMPORTANT: It is Life Science Alliance policy that if requested, original data images must be made available. Failure to provide original images upon request will result in unavoidable delays in publication. Please ensure that you have access to all original microscopy and blot data images before submitting your revision.*** Reviewer #1 (Comments to the Authors (Required)): It has been shown that the Fc receptor CD16 can bind to surface ligands in addition to immunoglobulins, triggering the activation of NK cells and ADCC. In this novel and interesting paper, Sconocchia and coll, used CD32-CAR T cells that they previously generated to identify putative surface ligands recognized by the Fc receptor CD32 on tumor cells. They examined 20 distinct cell types of which 15 were cancer cell lines and demonstrated that that CD32-CAR T cells recognize putative ligands on two triple negative cancer cell lines (MDA-MB-468 and MDA-MB-23), as well as other tumor cell lines, including HER2+ HCC-1954 cells, and CRC HT29. Importantly, CD32-CAR T cells did not recognize normal cell lines, such as primary fibroblasts and a myoblast cell line. The authors further performed differential gene expression analysis between cells positive and negative for CD32-CAR T cell recognition, identifying a number of potential candidate molecules. Finally, they showed that target cell expression of ICAM1 is essential for CD32-CAR T cells recognition. This is a brilliant application of a novel biosensor for the identification of CD32 unknown ligands. Moreover, this work has also led to demonstrate a role of CD32-CAR mediated cytotoxicity independent from ADCC which may be important for therapeutic avenues of intervention. The experiments are extensive and convincing. The paper is well-organized and written. I have only minor suggestions that the authors may consider 1. In introducing Fc Receptors it is unclear whether the authors are describing human or mouse Fc receptors. The authors should clarify this from the beginning 2. In the beginning of the results, the authors say that they purified T cells for scRNA seq. It is unclear from where these cells were purified. Thank you for submitting your revised manuscript entitled "Direct CD32 T cell cytotoxicity: implications for breast cancer prognosis and treatment.". We would be happy to publish your paper in Life Science Alliance pending final revisions necessary to meet our formatting guidelines.
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A. FINAL FILES:
These items are required for acceptance.
--An editable version of the final text (.DOC or .DOCX) is needed for copyediting (no PDFs).
--High-resolution figure, supplementary figure and video files uploaded as individual files: See our detailed guidelines for preparing your production-ready images, https://www.life-science-alliance.org/authors --Summary blurb (enter in submission system): A short text summarizing in a single sentence the study (max. 200 characters including spaces). This text is used in conjunction with the titles of papers, hence should be informative and complementary to the title. It should describe the context and significance of the findings for a general readership; it should be written in the present tense and refer to the work in the third person. Author names should not be mentioned.

B. MANUSCRIPT ORGANIZATION AND FORMATTING:
Full guidelines are available on our Instructions for Authors page, https://www.life-science-alliance.org/authors We encourage our authors to provide original source data, particularly uncropped/-processed electrophoretic blots and spreadsheets for the main figures of the manuscript. If you would like to add source data, we would welcome one PDF/Excel-file per figure for this information. These files will be linked online as supplementary "Source Data" files. **Submission of a paper that does not conform to Life Science Alliance guidelines will delay the acceptance of your manuscript.** **It is Life Science Alliance policy that if requested, original data images must be made available to the editors. Failure to provide original images upon request will result in unavoidable delays in publication. Please ensure that you have access to all original data images prior to final submission.** **The license to publish form must be signed before your manuscript can be sent to production. A link to the electronic license to publish form will be sent to the corresponding author only. Please take a moment to check your funder requirements.** **Reviews, decision letters, and point-by-point responses associated with peer-review at Life Science Alliance will be published online, alongside the manuscript. If you do want to opt out of having the reviewer reports and your point-by-point responses displayed, please let us know immediately.** Thank you for your attention to these final processing requirements. Please revise and format the manuscript and upload materials within 7 days.
Thank you for this interesting contribution, we look forward to publishing your paper in Life Science Alliance. Thank you for submitting your Research Article entitled "Direct CD32 T cell cytotoxicity: implications for breast cancer prognosis and treatment.". It is a pleasure to let you know that your manuscript is now accepted for publication in Life Science Alliance. Congratulations on this interesting work.
The final published version of your manuscript will be deposited by us to PubMed Central upon online publication.
Your manuscript will now progress through copyediting and proofing. It is journal policy that authors provide original data upon request.
Reviews, decision letters, and point-by-point responses associated with peer-review at Life Science Alliance will be published online, alongside the manuscript. If you do want to opt out of having the reviewer reports and your point-by-point responses displayed, please let us know immediately. ***IMPORTANT: If you will be unreachable at any time, please provide us with the email address of an alternate author. Failure to respond to routine queries may lead to unavoidable delays in publication.*** Scheduling details will be available from our production department. You will receive proofs shortly before the publication date. Only essential corrections can be made at the proof stage so if there are any minor final changes you wish to make to the manuscript, please let the journal office know now.

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You can contact the journal office with any questions, contact@life-science-alliance.org Again, congratulations on a very nice paper. I hope you found the review process to be constructive and are pleased with how the manuscript was handled editorially. We look forward to future exciting submissions from your lab.
Sincerely, Novella Guidi, PhD Scientific Editor Life Science Alliance