Results of a study reported at the Society for Immunotherapy of Cancer (SITC) Annual Meeting 2019 in National Harbor, Maryland, showed that specific “immunophenotypes” derived from imaging mass cytometry of tissue sections of specimens collected from patients with diffuse large B-cell lymphoma (DLBCL) were associated with patient outcome.1
The process of imaging mass cytometry uses a laser to scan tissue that has been labeled with metal-tagged antibodies or probes specific for certain cell types. Tissue vaporized by laser ablation is then analyzed by a mass cytometer. Notably, image mass cytometry allows for the spatial mapping of ablated tissue within the specimen at a subcellular resolution.
In this study, imaging mass cytometry was used to simultaneously investigate the spatial arrangement of cells comprising the tumor microenvironment (TME) of formalin-fixed paraffin-embedded (FFPE) tissue sections obtained from patients with DLBCL.1
An impetus for an investigation of the TME as a modulator of tumor response to immune checkpoint inhibitor therapy was the observation from a study of a programmed cell death-1 (PD-1) inhibitor in patients with DLBCL. This observation was that very few patients benefited from this treatment approach, even in the presence of high expression levels of programmed cell death-ligand 1 (PD-L1).2
In 41 microarray core specimens from 33 patients with DLBCL, 33% of the cells were immune cells. Of those immune cells, 36%, 30%, 26%, and 8% were classified as CD4 T-cells (CD4), CD8 T-cells (CD8), macrophages, and regulatory T-cells (TREG), respectively. Immune cell infiltration varied widely between specimens, with percentages ranging from 7% to 75%.
Interestingly, patients with tumors cells that coexpressed PD-L1, CC chemokine receptor 4 (CCR4), and T-cell immunoglobulin and mucin-domain containing-3 (TIM3) were shown to have longer overall survival compared with patients with tumor specimens lacking this protein expression pattern (P =.003).
Furthermore, an analysis of the spatial arrangement of 5 types of cells (ie, endothelial, TREG, CD4, macrophages, and tumor cells) with respect to their average distance from CD8 cells in the tumor specimens revealed that certain immune phenotypes were associated with refractory disease.
In their concluding remarks, the study authors noted that this “novel approach to spatial analysis of the immune architecture reveals clinically relevant insights into the TME.”1
- Hav M, Colombo A, Gerdtsson E, et al. Highly multiplexed single cell spatial analysis of the tumor microenvironment in lymphoma. Presented at: the Society for Immunotherapy of Cancer Annual Meeting; November 6-10, 2019; National Harbor, MD. Abstract P69.
- Ansell SM, Minnema MC, Johnson P, et al. Nivolumab for relapsed/refractory Diffuse Large B-Cell Lymphoma in patients ineligible for or having failed autologous transplantation: A single-arm, phase II study. J Clin Oncol. 2019;37(6):481–489.