The cellular ratio of immune tolerance (immunoCRIT) is a definite marker for aggressiveness of solid tumors and may explain tumor dissemination patterns

Abstract

The adaptive immune system is involved in tumor establishment and aggressiveness. Tumors of the ovaries, an immune-privileged organ, spread via transceolomic routes and rarely to distant organs. This is contrary to tumors of non-immune privileged organs, which often disseminate hematogenously to distant organs. Epigenetics-based immune cell quantification allows direct comparison of the immune status in benign and malignant tissues and in blood. Here, we introduce the "cellular ratio of immune tolerance" (immunoCRIT) as defined by the ratio of regulatory T cells to total T lymphocytes. The immunoCRIT was analyzed on 273 benign tissue samples of colorectal, bronchial, renal and ovarian origin as well as in 808 samples from primary colorectal, bronchial, mammary and ovarian cancers. ImmunoCRIT is strongly increased in all cancerous tissues and gradually augmented strictly dependent on tumor aggressiveness. In peripheral blood of ovarian cancer patients, immunoCRIT incrementally increases from primary diagnosis to disease recurrence, at which distant metastases frequently occur. We postulate that non-pathological immunoCRIT values observed in peripheral blood of immune privileged ovarian tumor patients are sufficient to prevent hematogenous spread at primary diagnosis. Contrarily, non-immune privileged tumors establish high immunoCRIT in an immunological environment equivalent to the bloodstream and thus spread hematogenously to distant organs. In summary, our data suggest that the immunoCRIT is a powerful marker for tumor aggressiveness and disease dissemination.

Simultaneous Statistical Inference for Epigenetic Data

“…Such a situation was present in [ 29 ]. In their study, a set of three pre-identified gene regions was considered.…”

Manipulation of regulatory T cells and antigen‐specific cytotoxic T lymphocyte‐based tumour immunotherapy

“…It appears that the peripheral tolerance has to be established before a metastatic cancerous growth takes place. In this regard, it is important to mention the report by Türbachova et al . on higher Treg cell ratio in peripheral blood tolerance and metastasis.…”

Novel technologies and emerging biomarkers for personalized cancer immunotherapy

“…This allows for a significantly broader range of acceptable sample conditions collected by clinical sites. By simply freezing and shipping the collected whole blood or tissue samples without any other additional steps, it allows for routine monitoring of patients and immune-monitoring during clinical trials, multicenter studies and retrospective studies as well as the comparison of results across different studies [ 157 , 158 ]. A common application of this standardized, epigenetic-based, immune diagnostic technology is monitoring cell-mediated immunity during immune-modulatory clinical trials for cancer patients or inflammatory diseases.…”