Comparative analysis of the tumor microenvironment in primary versus metastatic lymph node malignancies using The Cancer Genome Atlas data.

Abstract

e15189 Background: The tumor microenvironment (TME) plays a critical role in cancer progression, immune evasion, and metastatic spread. While lymph node involvement is a key prognostic factor across many malignancies, differences in the cellular composition of the TME between primary tumors and lymph node metastases remain incompletely characterized. We sought to systematically compare the immune and stromal landscapes of primary versus metastatic lymph node tumors using transcriptomic data from The Cancer Genome Atlas (TCGA). Methods: Gene expression data were obtained from the Genomic Data Commons (GDC) for lymph node pan-cancer samples classified as primary or metastatic. Data preprocessing and visualization were performed in R using the tidyverse. Statistical comparisons of xCell enrichment scores between primary and metastatic tumors were conducted using fixed-effects regression models implemented in the Fixest package, with adjustment for multiple comparisons. Results: Significant differences in tumor-associated cell populations were observed between primary (n = 510) and metastatic (n = 211) lymph node tumors across more than 40 cell types. Many immune and stromal populations demonstrated highly significant differences, with p-values far exceeding conventional thresholds (many p < 0.0001). Notably, multiple B-cell populations, including naïve B cells, memory B cells, class-switched memory B cells, and plasma cells, showed some of the strongest statistical differences (e.g., p < 0.0001). Significant differences were also observed among myeloid lineage cells, including granulocyte–macrophage progenitors and monocyte/macrophage subsets, as well as across multiple T-cell differentiation states. These findings indicate extensive and statistically robust remodeling of immune and stromal components in metastatic lymph node tumors. Conclusions: Our findings demonstrate widespread and significant alterations in the tumor microenvironment between primary and metastatic lymph node tumors. These results highlight the complexity of immune and stromal reprogramming during metastasis and may inform the future design of metastasis-specific immunomodulatory strategies.