Histology could predict a “hot” or a “cold” gastric tumor?

Abstract

44 Background: The emerging role of immunotherapy (IT) in cancer treatments has increased the research about tumor microenvironment (TME), tumor infiltrating lymphocytes (TILs) function and their TME regulation. Nowadays ongoing trial are showing conflicting preliminary data about the efficacy of IT in advanced gastric cancer (GC). Therefore, we performed this exploratory analysis to evaluate the correlation between histology, TILs density (reported as CD4/CD8 tissue ratio), neutrophil-lymphocytes ratio (NLR) and response outcome in GC patients who underwent cytotoxic neoadjuvant treatment (NAD). Methods: CD4+ and CD8+ expression was assessed by immunohistochemistry (IHC) in pre-NAD biopsies. NLR was calculated on baseline complete blood count. A cut-off value to define low or high NLR has been selected on 3.0, based on literature data. X2 test was used to explore the correlation between histology, CD4/CD8 ratio, NLR and response. Results: We analyzed 10 diffuse and 10 intestinal GC histotypes. In the intestinal-type CD4/CD8 ratio was lower (ratio range 1:15 - 1:20) with a predominant count of CD8+ suggesting a hot and inflamed TME compared to the diffuse cohort (ratio range 1:3 -1:5) where both CD8+ and CD4+ density was lower (p=0.03). Baseline NLR was calculated in 18 out of 20 pts. All intestinal GCs showed a low NLR (<3) while all diffuse GCs displayed a high cutoff (p=0.03). CD4/CD8 ratio resulted associated to histology (p=0.025) and response outcome (p=0.0003). NLR was statistically related to histology (p=0.03) and CD4/CD8 tissue ratio (p=0.03), confirming a different systemic inflammatory status and TME according to histology. Conclusions: Despite the small sample size, our exploratory analysis shows a possible correlation between histology, systemic inflammation and TME behavior (“hot” vs“cold”) described by NLR and TILs concentration (CD4/CD8 ratio) respectively and response to NAD. Intestinal-type seems to be a “hot” tumor whereas diffuse-type appears “cold”. Future clinical trial should analyze the impact of histology and TME features on IT efficacy and the appropriate strategy to convert “cold” tumor increasing TILs density.