Immune Cell–Cytokine Interplay in NSCLC and Melanoma: A Pilot Longitudinal Study of Dynamic Biomarker Interactions

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

In the results tables, place zeros, for example 0.981

One of the observations mentioned is that the criteria used in phenotype studies and cytokine detection are minimal, and the patient samples studied are also minimal—in some groups of 9 and in others, 7—to detect TNF-alpha, IL-2, and IL-10 with respect to the doses used. I know that it is somewhat difficult for these types of studies. The use of biological and immunological biomarkers with non-small cell lung cancer (NSCLC) and melanoma tracked at three time points would be a good start, but more time points are needed to clarify the benefit of immunotherapy.
Regarding the key parameters of PD-1 expression, CD-95 levels, CD8 T cell population, CTLA-4 cell expression, PD-1/CD95, CD8-CTLA-4, and CD8-CTLA-5, it is important to clarify the statistical studies used. Figures 4 and 5 show a very large standard error, indicating a significant variability. It is somewhat complicated to draw conclusions regarding the function of cytokines in this study, since they are related to cell cycle checkpoints. Further studies on IL-10 and TNF-alpha are needed, as the authors point out, to optimize immunology and checkpoint mechanisms, as well as resistance control in NSCLC and melanoma.

Comments on the Quality of English Language

The English language is accepted

Author Response

Please see attachment.

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

In this study, Grecea-Balaj et al. longitudinally investigated the expression of immune checkpoint markers on peripheral blood lymphocytes and serum cytokine levels from Nivolumab-treated NSCLC and melanoma patients. The authors aimed to identify key prognostic markers potentially associated with predicting patient survival outcomes. However, several points need to be clarified before publication of the manuscript in Immuno.

 

- It would be beneficial to have editorial support to correct typos and improve overall clarity.

 

- Please ensure all text is formatted with a uniform font family. This will greatly improve the readability and overall aesthetic quality of the manuscript.

 

- Some abbreviations were not defined in the main text. For clarity, it would be helpful to define all abbreviations at their first mention.

 

- Introduction: Although the background of the study is well described in the introduction section, it could be improved by clearly stating the specific objectives and scope of the study.

 

- Section 2: Please update the subheading numbers of Section 2.

 

- Section 3.1: It would be beneficial to provide graphs summarizing the data from Table 2 and Table 3 to present the author’s observations more efficiently.

 

- Table 2 and Table 3: Please provide representative FACS plots to show how the authors did immunophenotypic characterization of peripheral blood lymphocytes.

 

- Figures: Please ensure the unit is indicated on the y-axis label for better interpretation of the data and provide details about the statistical analysis, including significance test, the type of error bars (e.g., SD or SEM) and whether the values represent the mean or median in every figure legend.

 

- Figure 1 and Figure 2: If the figures represent serum cytokine levels, it would be helpful to clearly state that in the figure legend to make it easier for readers to understand.

 

- Discussion: Please cite the figure or table linked to its corresponding explanation in the text, as the current descriptions are not easy to follow.

Comments for author File: Comments.pdf

Author Response

Please see the attachment below.

Author Response File: Author Response.pdf

Reviewer 3 Report

Comments and Suggestions for Authors

The manuscript is fine. I have a few minor comments:

Tables 2 and 3: Numerical values should use a “.” instead of a comma “,”. For example, “37,3” should be corrected to “37.3”.

Tables 4, 5, and 6: Values should be presented with a zero before the decimal point, e.g., “0.34” instead of “.34”. Additionally, the authors should clarify the meaning of entries that contain only a “.” 

Comments on the Quality of English Language

ok

Author Response

Please see the attachment below. 

Author Response File: Author Response.pdf