Correlation Between Immune Lymphoid Cells and Plasmacytoid Dendritic Cells in Human Colon Cancer

Abstract

BackgroundInnate lymphoid cells (ILCs), so far studied mostly in mouse models, are important tissue-resident innate immune cells that play important roles in the colorectal cancer microenvironment and maintain mucosal tissue homeostasis. Plasmacytoid dendritic cells (pDCs) present complexity in various tumor types and are correlated with poor prognosis. pDCs can promote HIV-1–induced group 3 ILC (ILC3) depletion through the CD95 pathway. However, the role of ILC3s in human colon cancer and their correlation with other immune cells, especially pDCs, remain unclear.MethodsWe characterized ILCs and pDCs in the tumor microenvironment of 58 colon cancer patients by flow cytometry and selected three patients for RNA sequencing.ResultsILC3s were negatively correlated, and pDCs were positively correlated, with cancer pathological stage. There was a negative correlation between the numbers of ILC3s and pDCs in tumor tissues. RNA sequencing confirmed the correlations between ILC3s and pDCs and highlighted the potential function of many ILC- and pDC-associated differentially expressed genes in the regulation of tumor immunity. pDCs can induce apoptosis of ILC3s through the CD95 pathway in the tumor-like microenvironment.ConclusionsOne of the interactions between ILC3s and pDCs is via the CD95 pathway, which may help explain the role of ILC3s in colon cancer.

The Therapeutic Potential of Tackling Tumor-Induced Dendritic Cell Dysfunction in Colorectal Cancer

“…Strikingly, very few studies have focused on the different DC subsets, which present different functional specializations, in relation to CRC and to T cell function. For instance, infiltration by pDCs has yielded controversial results, with some studies associating pDCs infiltration with Treg development and poorer prognosis and others with increased survival, but without taking maturation status into account (155)(156)(157).…”

Current perspective on biological properties of plasmacytoid dendritic cells and dysfunction in gut

“…Cancer of the digestive system, specifically colon cancer, is associated with various clinicopathological characteristics. There is mounting evidence that the immune system may prevent the onset, progression, and metastatic diffusion of colorectal cancer (CRC) 135 . The host immune system can initiate an immune response against colon cancer cells, but tumor cells may utilize different strategies to avoid detection 136 …”

“…The amount of pDCs is connected to the pathological and clinical stages of the tumor 135 . The proportion of pDCs grew from proximal to distal, and the fraction of pDCs increased with the growth of the pathological stages of the tumor.…”

“…The frequency of ILC3 and pDCs in the tumor‐like microenvironment was negatively related using RNA‐Seq, suggesting the gene pDCs expressed may be involved in tumor growth or inhibition 138 . For instance, the upregulation of ARHGAP4, HSPD1, HNRNPA2B1, UBAP2L, STAG1, TUBB, GPX2, CD44, PEBP4 , and CD274 were associated with the progression, whereas the downregulation of SNAP23, PTPRE, RPS13 , and OGT were associated with the tumor suppression 135 . A patient population cohort analysis further indicated that the higher density of infiltrating pDCs, the better the overall survival of patients with colon cancer 139 …”

“…There is mounting evidence that the immune system may prevent the onset, progression, and metastatic diffusion of colorectal cancer (CRC). 135 The host immune system can initiate an immune response against colon cancer cells, but tumor cells may utilize different strategies to avoid detection. 136 pDCs have been implicated in the colonic tumor microenvironment, 23 but innate lymphoid cells (ILCs) can sustain mucosal integrity by generating powerful cytokines.…”