The Role of Immune Checkpoint Blockade in Acute Myeloid Leukemia

Round 1

Reviewer 1 Report

Dear editor:

The authors aimed to explore the functioning of immune checkpoint blockers along with the data of clinical trials and their outcomes in acute myeloid leukaemia (AML) patients during the past seven years. The manuscript is well structured in most parts, I only have a few comments:

1.       [Line 95-107] The authors need to add some statistical results (CR rate, OS, etc) to compare with other therapies to consolidate their conclusion that immunotherapy “has played a revolutionary role in lymphoid malignancies and multiple solid tumors treatment”

2.       In the introduction section, the authors only used sub-sections to respectively mention these therapies, but failed to describe previous studies that have combined these therapies for clinical trials. I think the authors can use an additional subsection to introduce studies that use combinations of these therapies in other cancers.

3.       [Line 207-210] “In this database, the keywords (Medical Subject Headings (MeSH) terms) used for the research will be “acute myeloid leukemia”, “treatment”, “Immune Checkpoint”, and “PD-1/PD-L1” and “CTLA-4”.”  The authors need to use a table to elaborate on how they use one or some of these keywords as a combination for each search.

4.       [Line 146-147] “When an APC binds to CTLA-4, IFN-γ, TNF-α and IL-2 production are reduced, and T-cell proliferation is suppressed.”   The commas are misleading, as CTLA-4 seems to be equivalent to IFN-γ, TNF-α and IL-2. But they are not.

Author Response

Dear Reviewer

Thank you so much for your contributions to increase manuscript quality.

Author Response File: Author Response.docx

Reviewer 2 Report

In this review, the authors make a state of the art of The role of Immune Checkpoint Blockade in Acute Myeloid Leukaemia (AML). The review is an interesting topic but was disjointed and quite difficult to read. Several points in the manuscript need to be clarified, rewritten or more developed.

 Major comments:

1. Lines 51-52: Figure 1 does not illustrate specific cytogenetic abnormalities. Figure 1 doesn’t bring more information for the readers than the text. The table with clinically relevant mutations in AML could be more informative and interesting.

2. From the "Introduction" the authors could distinguish a section " Immune system in AML”

3. Why were the descriptions of CTLA-4 and PD-1/PD-L1 included as a subsection for „Chemotherapy”?

4. I think it would be better to create a section for "AML Therapy". Then enter the following items: 1) Chemotherapy, 2) Allogeneic stem cell transplantation (Allo-SCT), and 3) Immunotherapy in AML (with the description of PD-1, CTLA-4). Lines 112-201 need to be improved.

5. The authors could also briefly describe therapeutic targeting of the macrophage immune checkpoint in AML.

6. The authors could also discuss the studies of pembrolizumab in AML.

7. Figure 3: Records screened n=25 and records excluded n=36. Are the numbers correct?

Author Response

Dear reviewer

Thank you so much for your contributions and suggestions to increase the manuscript quality.

Author Response File: Author Response.docx

Round 2

Reviewer 2 Report

I would like to thank the authors for taking my comments and suggestions into consideration and implementing them into the revised manuscript.