Title: The Current Status and Prospects of Gut Microbiota Combined with PD-1/PD-L1
Inhibitors in the Treatment of Colorectal Cancer: A Review
Version: 1 Date: 04 Mar 2025
Reviewer's report:
Deng and colleagues present a review of an important topic in the management of colorectal
cancer (CRC) with immune checkpoint blockade (ICB): the role of the gut microbiome in
modulating these responses to therapy. Unfortunately  in CRC  there are limited reports of the
role of the gut or tumoral microbiome affecting the efficacy of response to therapy as reflected
by their review here. As such I worry that there are groupings of studies combining gut and
tumoral microbial profiles as well as pMMR and dMMR CRC tumors. It is unclear to me that
these groupings can and should be made and that it may cloud the understanding of each of
these distinct biological processes. Additionally much of the text reviews well defined biologic
processes and does not focus on their very important and nuanced question of the role of the
microbiome in modulating responses to ICB.
Major Points:
1) Response to ICB in CRC outside of the clinical trial setting is almost completely limited to
dMMR CRC. This important distinction is blurred throughout the manuscript and especially
importantly so in the introduction of the work which inappropriately may lead one to assume
efficacy of ICB across CRC subtypes. Throughout the manuscript this delineation needs to be
made more clear.
2) The methods presented are that of a structured and systematic review while the majority of the
text does not delve into the 8 preclinical and 5 clinical studies but instead discusses incomplete
reviews of various other biological processes instead of focusing on the role of the tumoral and
gut microbiome in driving heterogeneity in response.
3) Be careful throughout the text to delineate the tumoral and gut microbiome. These two distinct
communities engage tumoral and host biology through very different processes.
Minor Points:
1) The review of the role of the microbiome in CRC in the introduction is extremely limited
and frankly outside the scope of a review focused on its role in modulating response to ICB.
There are innumerable reviews of the microbiome in CRC and if it is reviewed a more thorough
review would certainly be necessary if one is going to the detail of noting individual bacteria
and researchers.
2) Non-english text is included in Figure 1 severely limiting one's ability to review this presented
English language manuscript. Furthermore the caption presented includes instructions to the
author using a templated form and should have been removed. This degree of oversight is
unacceptable and calls the overall work into significant question.
3) Why is the country of study included in the clinical but not animal studies table?
4) Review of the mechanism of action and resistance of ICB seems well outside the scope of
this review. Moreover these sections are again incomplete in their review.
Title: The Current Status and Prospects of Gut Microbiota Combined with PD-1/PD-L1
Inhibitors in the Treatment of Colorectal Cancer: A Review
Version: 1 Date: 04 Mar 2025
Reviewer's report:
Deng and colleagues present a review of an important topic in the management of colorectal
cancer (CRC) with immune checkpoint blockade (ICB): the role of the gut microbiome in
modulating these responses to therapy. Unfortunately  in CRC  there are limited reports of the
role of the gut or tumoral microbiome affecting the efficacy of response to therapy as reflected
by their review here. As such I worry that there are groupings of studies combining gut and
tumoral microbial profiles as well as pMMR and dMMR CRC tumors. It is unclear to me that
these groupings can and should be made and that it may cloud the understanding of each of
these distinct biological processes. Additionally much of the text reviews well defined biologic
processes and does not focus on their very important and nuanced question of the role of the
microbiome in modulating responses to ICB.
Major Points:
1) Response to ICB in CRC outside of the clinical trial setting is almost completely limited to
dMMR CRC. This important distinction is blurred throughout the manuscript and especially
importantly so in the introduction of the work which inappropriately may lead one to assume
efficacy of ICB across CRC subtypes. Throughout the manuscript this delineation needs to be
made more clear.
2) The methods presented are that of a structured and systematic review while the majority of the
text does not delve into the 8 preclinical and 5 clinical studies but instead discusses incomplete
reviews of various other biological processes instead of focusing on the role of the tumoral and
gut microbiome in driving heterogeneity in response.
3) Be careful throughout the text to delineate the tumoral and gut microbiome. These two distinct
communities engage tumoral and host biology through very different processes.
Minor Points:
1) The review of the role of the microbiome in CRC in the introduction is extremely limited
and frankly outside the scope of a review focused on its role in modulating response to ICB.
There are innumerable reviews of the microbiome in CRC and if it is reviewed a more thorough
review would certainly be necessary if one is going to the detail of noting individual bacteria
and researchers.
2) Non-english text is included in Figure 1 severely limiting one's ability to review this presented
English language manuscript. Furthermore the caption presented includes instructions to the
author using a templated form and should have been removed. This degree of oversight is
unacceptable and calls the overall work into significant question.
3) Why is the country of study included in the clinical but not animal studies table?
4) Review of the mechanism of action and resistance of ICB seems well outside the scope of
this review. Moreover these sections are again incomplete in their review.
Please review this paper.
user
Title: The Current Status and Prospects of Gut Microbiota Combined with PD-1/PD-L1
Inhibitors in the Treatment of Colorectal Cancer: A Review
Version: 1 Date: 04 Mar 2025
Reviewer's report:
Deng and colleagues present a review of an important topic in the management of colorectal
cancer (CRC) with immune checkpoint blockade (ICB): the role of the gut microbiome in
modulating these responses to therapy. Unfortunately  in CRC  there are limited reports of the
role of the gut or tumoral microbiome affecting the efficacy of response to therapy as reflected
by their review here. As such I worry that there are groupings of studies combining gut and
tumoral microbial profiles as well as pMMR and dMMR CRC tumors. It is unclear to me that
these groupings can and should be made and that it may cloud the understanding of each of
these distinct biological processes. Additionally much of the text reviews well defined biologic
processes and does not focus on their very important and nuanced question of the role of the
microbiome in modulating responses to ICB.
Major Points:
1) Response to ICB in CRC outside of the clinical trial setting is almost completely limited to
dMMR CRC. This important distinction is blurred throughout the manuscript and especially
importantly so in the introduction of the work which inappropriately may lead one to assume
efficacy of ICB across CRC subtypes. Throughout the manuscript this delineation needs to be
made more clear.
2) The methods presented are that of a structured and systematic review while the majority of the
text does not delve into the 8 preclinical and 5 clinical studies but instead discusses incomplete
reviews of various other biological processes instead of focusing on the role of the tumoral and
gut microbiome in driving heterogeneity in response.
3) Be careful throughout the text to delineate the tumoral and gut microbiome. These two distinct
communities engage tumoral and host biology through very different processes.
Minor Points:
1) The review of the role of the microbiome in CRC in the introduction is extremely limited
and frankly outside the scope of a review focused on its role in modulating response to ICB.
There are innumerable reviews of the microbiome in CRC and if it is reviewed a more thorough
review would certainly be necessary if one is going to the detail of noting individual bacteria
and researchers.
2) Non-english text is included in Figure 1 severely limiting one's ability to review this presented
English language manuscript. Furthermore the caption presented includes instructions to the
author using a templated form and should have been removed. This degree of oversight is
unacceptable and calls the overall work into significant question.
3) Why is the country of study included in the clinical but not animal studies table?
4) Review of the mechanism of action and resistance of ICB seems well outside the scope of
this review. Moreover these sections are again incomplete in their review.
assistant