Immunomethylomics: A Novel Cancer Risk Prediction Tool

Abstract

There is emerging evidence that the immune biology associated with lung and other solid tumors, as well as patient immune genetic traits, contributes to individual survival. At this time, dramatic advances in immunologic approaches to the study and management of human cancers are taking place, including lung and head and neck squamous cell carcinoma. However, major obstacles for therapies are the profound immune alterations in blood and in the tumor microenvironment that arise in tandem with the cancer. Although there is a significant current effort underway across the cancer research community to probe the tumor environment to uncover the dynamics of the immune response, little similar work is being done to understand the dynamics of immune alterations in peripheral blood, despite evidence showing the prognostic relevance of the neutrophil/lymphocyte ratio for these cancers. A prominent feature of cancer-associated inflammation is the generation of myeloid-derived suppressor cells, which arise centrally in bone marrow myelopoiesis and peripherally in response to tumor factors. Two classes of myeloid-derived suppressor cells are recognized: granulocytic and monocytic. To date, such immune factors have not been integrated into molecular classification or prognostication. Here, we advocate for a more complete characterization of patient immune profiles, using DNA from archival peripheral blood after application of methylation profiling (immunomethylomics). At the heart of this technology are cell libraries of differentially methylated regions that provide the "fingerprints" of immune cell subtypes. Going forward, opportunities exist to explore aberrant immune profiles in the context of cancer-associated inflammation, potentially adding significantly to prognostic and mechanistic information for solid tumors.

Prediagnostic Immune Cell Profiles and Breast Cancer

“…21,22 Using such deconvolution, methylation-derived leukocyte profiles, including the methylation-derived neutrophil-to-lymphocyte ratio (mdNLR), have been shown to be altered in patients with a variety of cancers and appear to be associated with cancer prognosis. [27][28][29][30][31][32][33] Recently, among a small population of heavy smokers, the mdNLR was reported to be altered years before a lung cancer diagnosis, supporting the hypothesis that circulating leukocyte profiles may be markers of cancer risk. 34 Here, we use prospectively collected peripheral blood samples from a large, nationwide cohort of women and report associations between methylation-derived leukocyte profiles and breast cancer risk.…”

Clinical significance of tumor-infiltrating lymphocytes and neutrophil-to-lymphocyte ratio in patients with stage III colon cancer who underwent surgery followed by FOLFOX chemotherapy

“…The role of cellular-mediated inflammatory response in carcinogenesis, which can be represented as lymphocytes, neutrophils, and monocytes in the complete blood cell count, is known to be important 11,12 . The neutrophil-to-lymphocyte ratio (NLR) is a widely used prognostic marker of various tumors including colorectal cancer 13–15 .…”

Prognostic impact of persistent lower neutrophil-to-lymphocyte ratio during preoperative chemoradiotherapy in locally advanced rectal cancer patients: A propensity score matching analysis

“…[ 7 ] These myeloid-derived suppressor cells (MDSCs) suppress host immune cells through various pathways and could diminish lymphocytes. [ 8 ] NLR could be used to estimate the relative balance of myeloid and lymphocytic lineages, thus reflecting host immunity in cancer patients. [ 8 ] The prognostic impact of NLR was thoroughly investigated in different types of diseases including gastric cancer, hepatocellular cancer, pancreatic cancer, head and neck cancer, esophageal cancer, breast cancer, and thyroid cancer.…”