Review for 10.1186/s12876-024-03168-0 (2024)

Title: Association of lymphocyte subsets with the efficacy and prognosis of PD#1 inhibitor
therapy in advanced gastric cancer: results from a monocentric retrospective study
Version: 0 Date: 27 Sep 2023
Reviewer's report:
During the last years, immunotherapy has become part of the treatment armamentarium for
gastric cancer (GC). Nevertheless, not all GC patients do respond, and most of them will
ultimately progress. Thus, studies trying to better identify immune-sensitive GC populations
are needed. As the authors stated, the analysis of circulating immune populations is easy and
feasible, and could serve as a biomarker of response. Wang et al. have done a very good effort
in this regard. Nevertheless, different methodology aspects need to be better addressed in order
to homogenize and make more credible their results. I encourage the authors to readdress all the
issues and to improve their investigations.
Authors are mixing patients receiving chemo + immunotherapy vs. other schemas without
chemotherapy. Considering the possible effect of the chemotherapy on the lymphocytes, patients
receiving chemo should be considered separately from patients not receiving chemotherapy.
Moreover, authors are mixing patients treated at different treatment lines. Lymphocytes
populations may vary depending on if patients are naïve of treatment or not. I would recommend
analyze separately patients on first line from the others.
Authors identify the concept “immunotherapy efficacy” with “best response”. However,
“immunotherapy efficacy” is an ambiguous concept that also accept longer survivors, for
example. I would be more precise, and specify “best response”.
Authors define dMMR as the loss of a minimum of one of the MMR protein. Nevertheless, when
only one protein is lost, the dMMR diagnosis is unclear and should be confirmed by PCR.
There are nine (out of 195) patients with dMMR. To be fair, these patients should be considered
a part from the pMMR as they represent a very different disease population.
It is not clear if analyses are univariate or multivariate, and the credibility of the results may
differ depending on this fact (Table 2).
Authors present statistically differnces on PFS due to a p value of < 0.05. Nevertheless, when
looking at the numbers, these differences consider less than one month (except when comparing
pMMR and dMMR tumors). Thus, these differences are not clinically significant nor relevant.
Minor comments
The second sentence of introduction should be referred.
Status of MMR is not an expensive test.
In the last paragraph of the introduction, the authors talk about the prognostic role of the blood
lymphocytes, although this role is not analyzed within this study, as all patients are treated with
immunotherapy… so only the predictive role is analyzed.
Authors should specify what “extensive metastases” means.
Authors reported that peripheral blood lymphocytes subsets were tested at initial diagnosis of
advanced disease (in patients treated with immunotherapy in second or further lines), before
immunotherapy and after three cycles. Nevertheless, there is no report of the test done “at initial
diagnosis of advanced disease”.
When reporting age, please insert the range (table 1).