Title: A novel immune checkpoint score system for prognostic evaluation in pancreatic
adenocarcinoma
Version: 2 Date: 03 Jan 2023
Reviewer's report:
Review of A novel immune checkpoint score system for prognostic evaluation in pancreatic
adenocarcinoma  by Chen, et al.
This manuscript attempts to identify a pathologic/molecular scoring system designed to predict
immune checkpoint inhibitor response.
1. While this is an important goal and the authors are to be commended on the large amount of
data generated, this manuscript is observatory in nature and does not achieve the stated goal.
I recommend that this manuscript not be accepted for the following major fundamental flaws
include:
2. Figure 1. data. Can the authors verify the comparison is 123 tumor and matched normal
pancreas from the TCGA database?  Is the “normal” from adjacent pancreatic tissue? Are the
samples paired? If so, the analysis should reflect this. Since this is a fundamental experiment
upon which all subsequent work is conducted, this must be verified with original data linking
these samples.
3. Fig 2 and 3 shows survival outcome data for the  patients from with the TCGA was obtained
and the authors report having “clinical data” for these samples. What other therapy was received?
Was chemotherapy given before or after surgery? What is the follow up time? Is it sufficient for
KM analysis of 63 patients? These data are critical for interpreting the results and the meaning
of any molecular findings or building the nomogram in Figure 4.
4. Figure 4. The clinicopathologic factors include metastatic disease (M) which suggests a highly
heterogeneous clinical group not suitable for this analysis.  Additionally, the hazard ratio for
outcome events for metastasis is less significant than tumor size (T) which also is inconsistent
with the literature.
5. Figure 10,11. The methods and images suggest protein expression levels of OX40L were
measured, but the abstract states transcripts. This is unclear and misleading for the reader.
Additionally, the samples used in these studies are clinically distinct from those used for the prior
experiments with no data regarding additional therapy so survival outcomes are not particularly
comparable.
6. There are no experiments or clinical data that actually prove, or even suggest, that the gene or
protein signatures identified will indeed predict tumor response to immune check point inhibitor
therapy.
Title: A novel immune checkpoint score system for prognostic evaluation in pancreatic
adenocarcinoma
Version: 2 Date: 03 Jan 2023
Reviewer's report:
Review of A novel immune checkpoint score system for prognostic evaluation in pancreatic
adenocarcinoma  by Chen, et al.
This manuscript attempts to identify a pathologic/molecular scoring system designed to predict
immune checkpoint inhibitor response.
1. While this is an important goal and the authors are to be commended on the large amount of
data generated, this manuscript is observatory in nature and does not achieve the stated goal.
I recommend that this manuscript not be accepted for the following major fundamental flaws
include:
2. Figure 1. data. Can the authors verify the comparison is 123 tumor and matched normal
pancreas from the TCGA database?  Is the “normal” from adjacent pancreatic tissue? Are the
samples paired? If so, the analysis should reflect this. Since this is a fundamental experiment
upon which all subsequent work is conducted, this must be verified with original data linking
these samples.
3. Fig 2 and 3 shows survival outcome data for the  patients from with the TCGA was obtained
and the authors report having “clinical data” for these samples. What other therapy was received?
Was chemotherapy given before or after surgery? What is the follow up time? Is it sufficient for
KM analysis of 63 patients? These data are critical for interpreting the results and the meaning
of any molecular findings or building the nomogram in Figure 4.
4. Figure 4. The clinicopathologic factors include metastatic disease (M) which suggests a highly
heterogeneous clinical group not suitable for this analysis.  Additionally, the hazard ratio for
outcome events for metastasis is less significant than tumor size (T) which also is inconsistent
with the literature.
5. Figure 10,11. The methods and images suggest protein expression levels of OX40L were
measured, but the abstract states transcripts. This is unclear and misleading for the reader.
Additionally, the samples used in these studies are clinically distinct from those used for the prior
experiments with no data regarding additional therapy so survival outcomes are not particularly
comparable.
6. There are no experiments or clinical data that actually prove, or even suggest, that the gene or
protein signatures identified will indeed predict tumor response to immune check point inhibitor
therapy.
Please review this paper.
user
Title: A novel immune checkpoint score system for prognostic evaluation in pancreatic
adenocarcinoma
Version: 2 Date: 03 Jan 2023
Reviewer's report:
Review of A novel immune checkpoint score system for prognostic evaluation in pancreatic
adenocarcinoma  by Chen, et al.
This manuscript attempts to identify a pathologic/molecular scoring system designed to predict
immune checkpoint inhibitor response.
1. While this is an important goal and the authors are to be commended on the large amount of
data generated, this manuscript is observatory in nature and does not achieve the stated goal.
I recommend that this manuscript not be accepted for the following major fundamental flaws
include:
2. Figure 1. data. Can the authors verify the comparison is 123 tumor and matched normal
pancreas from the TCGA database?  Is the “normal” from adjacent pancreatic tissue? Are the
samples paired? If so, the analysis should reflect this. Since this is a fundamental experiment
upon which all subsequent work is conducted, this must be verified with original data linking
these samples.
3. Fig 2 and 3 shows survival outcome data for the  patients from with the TCGA was obtained
and the authors report having “clinical data” for these samples. What other therapy was received?
Was chemotherapy given before or after surgery? What is the follow up time? Is it sufficient for
KM analysis of 63 patients? These data are critical for interpreting the results and the meaning
of any molecular findings or building the nomogram in Figure 4.
4. Figure 4. The clinicopathologic factors include metastatic disease (M) which suggests a highly
heterogeneous clinical group not suitable for this analysis.  Additionally, the hazard ratio for
outcome events for metastasis is less significant than tumor size (T) which also is inconsistent
with the literature.
5. Figure 10,11. The methods and images suggest protein expression levels of OX40L were
measured, but the abstract states transcripts. This is unclear and misleading for the reader.
Additionally, the samples used in these studies are clinically distinct from those used for the prior
experiments with no data regarding additional therapy so survival outcomes are not particularly
comparable.
6. There are no experiments or clinical data that actually prove, or even suggest, that the gene or
protein signatures identified will indeed predict tumor response to immune check point inhibitor
therapy.
assistant