Review for 10.1186/s12876-025-03862-7 (2025)

Title: Immunohistochemical Expression of PD-L1 in Colorectal Carcinoma Among Black
Patients and the Clinicopathological Correlates: A Cross-Sectional Study
Version: 2 Date: 14 Mar 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-While the study involves 96 CRC cases, this sample size may be considered small for
generalizing results across the entire Black population in Nigeria. Larger, multicenter studies
with more diverse samples could enhance the reliability and external validity of the findings.
-The study is conducted in Nnewi, a specific region in southeastern Nigeria. While this provides
valuable insights into the local population, the findings may not be fully generalizable to the
entire Nigerian population, especially considering the socio-economic and regional healthcare
differences. A more geographically diverse sample would improve the representativeness of the
results.
-The study uses a cross-sectional design, which means it provides a snapshot rather than tracking
changes over time. Longitudinal studies could offer more insight into how PD-L1 expression
changes over the course of disease progression and treatment, which is particularly relevant
when considering the role of immune checkpoint inhibitors.
-The study focuses on pathological characteristics and PD-L1 expression but does not
delve deeply into treatment outcomes or patient responses to therapies like anti-PD-1/PD-L1
inhibitors. It would be useful to explore how PD-L1 expression correlates with clinical outcomes
(e.g., survival rates, metastasis, or response to immune therapy), which could provide a more
comprehensive understanding of its prognostic value.
-The study mentions that three pathologists independently reviewed the slides, but it would
be helpful to discuss how discrepancies between the pathologists were resolved. Although
inter-observer variability is addressed by averaging scores, providing details on the consistency
between the pathologists (e.g., intra-class correlation or agreement) could strengthen the study's
reliability.
-The discussion frequently compares the study’s findings with other research but could provide
a more detailed analysis of why the differences in PD-L1 expression occur across regions. While
some potential explanations are offered (e.g., antibody differences, scoring methods), further
elaboration on the molecular or genetic differences between populations, such as variations in
immune responses or genetic predispositions, would be valuable.
-The study found no significant correlation between PD-L1 expression and age or gender, but the
discussion largely glosses over this finding. It could be expanded to discuss why this might be
the case, especially in the context of existing literature where PD-L1 expression has been linked
to younger age or male gender. A deeper analysis of potential underlying mechanisms (e.g., sex
hormones, genetic factors, or immune response differences) could provide more insight.
-While the discussion mentions that tumor microenvironment factors, such as tumor-infiltrating
lymphocytes (TILs) and immune-suppressive factors, may influence PD-L1 expression, this is
not explored in detail. Given the importance of TME in cancer progression and immune evasion,
a more thorough examination of how TME characteristics could be related to PD-L1 expression
would strengthen the discussion. For example, exploring how inflammatory markers or immune
cell composition in Nigerian CRC patients may differ from those in other regions could be
insightful.
-The discussion highlights PD-L1 expression as a promising marker for CRC prognosis and
immunotherapy eligibility but does not critically address the limitations or challenges associated
with using PD-L1 as a sole predictor of treatment response. There is growing evidence that PD-
L1 expression alone may not fully predict clinical outcomes or response to immune checkpoint
inhibitors (e.g., tumor mutational burden, microsatellite instability). A balanced discussion
acknowledging these complexities could enhance the robustness of the argument.