Characterization of the Tumor Immune Microenvironment in Lung Squamous Cell Carcinoma Using Imaging Mass Cytometry

Abstract

BackgroundLung squamous cell carcinoma (LUSC) is a major subtype of non-small cell lung cancer. The tumor immune microenvironment (TIME) affects the anti-tumor immune response and the patient’s prognosis, although the TIME in LUSC patients is incompletely understood.MethodsWe retrospectively collected surgical specimens from patients with previously untreated primary LUSC. Histopathological examination was used to identify tumor regions and adjacent regions, and imaging mass cytometry was used to characterize the immune cells in those regions. The results were compared between regions and between patients.ResultsWe identified heterogeneity in the TIME on comparing different patients with LUSC, although the tumor region and adjacent region both exhibited an immune response to the tumor. The TIME typically included a large number of infiltrating and activated T-cells, especially CD8+ T-cells, which closely interacted with the tumor cells in the tumor region. There was limited infiltration of B-cells, NK cells, and NKT cells, while the major immune suppressor cells were CD33+ myeloid-derived cells. We also identified a novel population of CD3−CD4+ cells with high expression of Foxp3 and TNFα, which might modulate the tumor microenvironment and play a proinflammatory role in the TIME.ConclusionsThe TIME of LUSC appears to be immunogenic and heterogenous, with predominant infiltration of activated CD8+ T-cells. The interactions between the tumor cells and T-cells facilitate the anti-tumor activity. A novel subpopulation of CD3−CD4+ cells with high TNFα and Foxp3 expression may modulate the tumor microenvironment and play a proinflammatory role.

Multiplex Tissue Imaging: Spatial Revelations in the Tumor Microenvironment

“…The data table integrates single ion signals per pixel, after which image and single cell segmentation can be converted to single-cell data for downstream analysis. In cancer research, IMC is used to discover novel phenotypes and biomarkers, or to study TME heterogeneity [22][23][24][25][30][31][32]36,43,44,50]. IMC is also used to predict prognosis and therapy responses in humans or in mice [23,30,51,[65][66][67][68][73][74][75].…”

“…Imaging strategies with multiplex antibody panels enable the discovery of novel (immune) phenotypes in the TME: for example, the discovery of one new immune subpopulation, identified as CD3 − CD4 + , in both the tumor region and the adjacent tumor area in primary squamous cell lung carcinomas that did not receive any therapy [24]. Interestingly, these CD3 − CD4 + immune cells expressed forkhead box P3 (FOXP3), terminal deoxynucleotidyl transferase (TdT), and tumor necrosis factor alpha (TNFα), but lacked expression of CD25, CD127, and interferon gamma (IFNγ).…”

Application of High-Throughput Imaging Mass Cytometry Hyperion in Cancer Research

“…In lung squamous cell carcinoma, Li et al. also found a new subpopulation of CD3− CD4+ cells with high level of TNFa and Foxp3 which could modify the TME and play a proinflammatory role ( 24 ). Aoki et al.…”

Histological changes associated with laser interstitial thermal therapy for radiation necrosis: illustrative cases

“…The immune cell composition of brain metastases is being increasingly studied and has been shown to contain a high number of lymphocytes subtypes of which can be influenced by local microenvironment and type of malignancy. [28][29][30][31][32] Immune regulatory molecules driving myeloid and lymphocytic cells (CD40L, IL6R, INHBA, AREG) are highly expressed, with specific increase in autoimmune inflammation mediators and specific enrichment of IL6 in microglia and TREM1 in microglia/macrophages. 28 RN histology also demonstrates marked inflammatory changes with abundant infiltration by CD3 1 T cells and CD68 1 macrophages but drivers of this process have been less well studied.…”