Application of theAMOCATIR workflow to tumor transcriptomic data delineates the adverse effect of immune cell infiltration in immune-privileged organs

Abstract

ABSTRACTImmune cells are present inside tumor tissue and can alter tumor growth. Expression profiles of human tumors hold transcripts from cancer cells and their microenvironment, including the infiltrating immune cells. Few standardized methods examine tumor immunobiology relying only on tumor transcriptome data. Using a new in-house developed R analysis workflow calledAMOCATI, we classified 43 cancer types from 11,176 patients according to the degree of infiltration by 18 distinct immune cell subsets, measured by the abundance of their transcriptomic signature, and calculated its effect on the disease outcome. In about half of cancers affecting organs without immune privilege, immune cell infiltration has beneficial effects. In contrast, immune infiltration in cancers of immune-privileged organs (eye, testis and brain) confers poor prognosis. Moreover, transcriptional evidence of increased immune cell activity in immune-privileged cancer sites is associated with bad prognosis. Thus, our results suggest that the effect of immune infiltration may depend on the origin of the primary tumor.SIGNIFICANCEOur in-house developed computational R approachAMOCATIallows to easily download public transcriptomic and clinical data, classify and analyze them.AMOCATI permitted us to define gene expression signatures associated with short- or long-term survival from 11,176 untreated patient unsorted biopsies in 43 types of cancer.We present the level of infiltration of 18 types of immune cell subsets transcriptomic signatures and 50 immune-related pathways in all these cancersCorrelation between immune infiltration of the tumor and survival establishes a link between tumor tissue of origin and the overall effect of immune infiltration on survival.Immune cell infiltration in tumors from ‘immune privileged organs’ correlate with shorter survival.Contrary to what we observe in ‘hot’ tumors, biological pathways of immune response are associated with a short-term survival profile in these cancers.