CELL: Can TREM2 enhance tumor anti-PD-1 immunotherapy?

Checkpoint immunotherapy is used to control T-cells on tumors, but the effect is destroyed by immunosuppressed myelin cells.
TREM2 is a myeloid receptacle that transmits in-cell signals and maintains a small glial response during Alzheimer's disease.
TREM2 is also expressed by tumor-soaked macrophages.
Recently, researchers at CELL reported that Trem2-/-mice were more resistant to the growth of various cancers than wild mice, and that Trem2-/-mice were more responsive to PD-1 immunotherapy.
addition, when used in association with anti-PD-1, treatment with monoclonal antibodies against TREM2 inhibits tumor growth and promotes degeneration.
single-cell seq (scRNA-seq) showed that TREM2 deficiency and anti-TREM2 were associated with rare MRC1 plus and CX3CR1 plus macrophages in tumor immersion, parallel to the expansion of bone marrow sub-groups that expressed immune stimulation factors, which promoted the improvement of T-cell response.
to tap into the significance of the discovery in human tumors, the researchers first used the IHC to analyze the expression of TREM2 protein in macrophages from normal human and tumor specimens.
With the exception of small glial cells, MITF-placental macrophages, endometrial macrophages, and al frescular macrophages, the expression of TREM2 was not detected in the vast majority of macrophages in the outer tissue.
contrast, the researchers observed TREM2 plus macrophages in 75 percent of tumors from different primary sites by screening and evaluating multicance tissue chips with 126 samples.
to avoid potential tumor heterogoglycity, the researchers further expanded the analysis to include complete tissue slices from 99 tumor samples, including tumors from many sites.
researchers have confirmed that TREM2 plus macrophages are present in almost all cases.
, the researchers explored the correlation between TREM2 expression and clinical outcomes in the Cancer Genome Atlas database.
set a threshold of 75% of the digits, the TREM2 expression is related to the worse total lifetime in the CRC queue.
in the TNBC queue, with a 75 percent scale cut-off point, treM2 expressions were also associated with worse total lifetimes and non-recurrence periods.
similar results were obtained by using the median expression of TREM2.
interestingly, in TNBC's multivariable survival analysis, TREM2 had additional survival prognosis independent of other myelin genes, indicating a direct contribution to the pathogenesis.
The correlation between TREM2 and macrophage characteristic genes was also shown in other types of human tumors, but the correlation between TREM2 expression and the overall or non-recurrence survival of patients was not significant, suggesting that TREM2's effect on tumor-invested macrophages and tumor immune responses may be specific.
, TREM2 is a potential target for altering bone marrow immersion in tumors and may enhance checkpoint immunotherapy.
.