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Cancers
Volume 15
Issue 10
10.3390/cancers15102696
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Article
Peer-Review Record

Development and Validation of Blood-Based Predictive Biomarkers for Response to PD-1/PD-L1 Checkpoint Inhibitors: Evidence of a Universal Systemic Core of 3D Immunogenetic Profiling across Multiple Oncological Indications

Cancers 2023, 15(10), 2696; https://doi.org/10.3390/cancers15102696
by Ewan Hunter 1, Matthew Salter 1, Ryan Powell 1, Ann Dring 1, Tarun Naithani 1, Maria Eleni Chatziioannou 1, Abel Gebregzabhar 1, Mutaz Issa 1, Jayne Green 1, Serene Ng 2, Chun Ren Lim 2, Cheah Soon Keat 3,4, Ang Tick Suan 3, Rakesh Raman 3, Ho Kean Fatt 3, Fabian Lee Wei Luen 3, Heba Alshaker 5, Dmitri Pchejetski 5, Dave Blum 6, Thomas Guiel 6, Robert Heaton, Jr. 6, Jedd Levine 6 and Alexandre Akoulitchev 1,*add Show full author list remove Hide full author list
Reviewer 1: Anonymous
Reviewer 3:
Anupam Kotwal
Cancers 2023, 15(10), 2696; https://doi.org/10.3390/cancers15102696
Submission received: 3 April 2023 / Revised: 6 May 2023 / Accepted: 8 May 2023 / Published: 10 May 2023
(This article belongs to the Topic Biomarker Development and Application)

Round 1

Reviewer 1 Report

No particular correction/implementations needed.

The paper is good for publication

Author Response

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Author Response File: Author Response.docx

Reviewer 2 Report

The manuscript from E Hunter et al describes a very preliminary assessment on the potential of a 3D genomic approach to identify patients receiving major benefit from Immune checkpont treatment of human cancer

The experimental design is sound but the study interpretation is limited by the quite low population of enrolled patients as well as their heterogeneity making the risk of bias quite high.

Moreover it is is hard to coceptualize how PBMNC nuclei 3D genomics can capture factors driving ICI inhibitors sensitivity which are related to the immune microenvironment in the tumor tissue and lymphoid organs as well as in tumor burden and quality of mutation which may activate the immune system. Thiese points need wider discussion, as well as some additional details on follow up studies  to reach a validated biomarker status need to be provided in the revised version.

In any case an interesting paper to quickly improve in clarifying the proof of concept clinical relevance

The in silico work is of true interest

Author Response

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Author Response File: Author Response.docx

Reviewer 3 Report

Well-conducted prospective observational study of biospecimens from n=229 undergoing treatment with immune checkpoint inhibitors for cancer, to develop a biomarker model for response to immune checkpoint therapy which achieved a high accuracy of 85%, sensitivity of 93% and specificity of 82%. Novel and important results with high likelihood of translation to clinical care. 

Author Response

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Author Response File: Author Response.docx

Round 2

Reviewer 2 Report

The paper has been correctly revised

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