PBMCs as Tool for Identification of Novel Immunotherapy Biomarkers in Lung Cancer
, Francesca Iommelli 2,†, Viviana De Rosa 2,*, Giuseppe Ercolano 3, Federica Sodano 3, Concetta Tuccillo 1, Luisa Amato 1, Virginia Tirino 4,5, Annalisa Ariano 1, Flora Cimmino 6, Gaetano di Guida 1, Gennaro Filosa 1, Alessandra di Liello 1, Davide Ciardiello 7, Erika Martinelli 1, Teresa Troiani 1, Stefania Napolitano 1, Giulia Martini 1, Fortunato Ciardiello 1, Federica Papaccio 8, Carminia Maria Della Corte 1,*,‡add
Show full author list
Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsThe manuscript identifies PBMCs as biomarkers for response to immunotherapy in lung cancer, they specially focus on cGAS-STING signaling. I have some concerns:
1. Using PBMCs as biomarkers to evaluate the effect of immunotherapy is reasonable in some way, since PBMCs are quiet heterogeneous, the results would be more meaningful if they could focus on a specific subset.
2. Some parts of the results should be moved to the introduction.
3. Limited sample size is a major shortcoming of the article, the author should include more samples in their research.
4. As mentioned above, the cell source of CXCL10 should be detected, and the mechanism study of cGAS-STING signaling in cytokine production is needed.
5. Correlation analysis of serum cytokine level and cGAS-STING signaling activation should be done.
6. Animal study should be used to evaluate the effect of DNA-PK Inhibitor in increasing effect of anti-PDL1
7. In Figure 5, in NR patients, the CXCL10 expression is higher than the R patients, while Figure 3 showed opposite results, the discrepancy should be explained.
8. The discussion section should further emphasize the value and novelty of the current study should be d here.
9. Fonts size in figures should be identical.
Author Response
Please see the attachment
Author Response File: 
Author Response.pdf
Reviewer 2 Report
Comments and Suggestions for AuthorsDe Rosa et al set out to determine if cGAS-STING signaling in isolated PMBCs isolated from NSCLC and SCLC patients can be used as biomarkers for predicting immunotherapy response. This is a important questions and the authors proved some interesting data supporting this hypothesis. However, a few issues limit enthusiasm for this report.
Major Issues
Sample sizes are small. While oftentimes the authors cannot control the availability of samples, they should discuss this as a limitation in the discussion.
The NCI-H661 cell line was derived from a large cell carcinoma patient (Phelps, et al. JBC, 1996), making its inclusion in this study confusing. A larger panel of SCLC and NSCLC cell lines should be tested.
Minor Points
Reference missing on line 284
The discussion should include the applicability of these results to transformed SCLC which is derived from NSCLC.
Author Response
Please see the attachment
Author Response File: Author Response.pdf
Round 2
Reviewer 1 Report
Comments and Suggestions for AuthorsAll concerns resolved.
Reviewer 2 Report
Comments and Suggestions for AuthorsAll comments addressed. Thank you to the authors for their revision.
