Immunologic constant of rejection
The Immunologic Constant of Rejection (ICR), is a set of genes that is involved in tissue destruction along a diverse set of physiological circumstances like autoimmune disease or allograft rejection or pathological conditions like infection and cancer.[1]
Important geneset within the ICR consist of:[2]
- T helper type 1 (Th1) cell-related factors such as Interferon Gamma (IFNG) and signal transducers and activator of transcription 1 (STAT1), Interleukine 12 (IL12),Interferon-regulatory factor 1 (IRF1), the transcription factor T-bet (TBX21).
- Immune effector or cytotoxic factors like the granzymes (GZMA, GZMB, GZMH perforin PRF1, and granulysin GNLY)
- Chemokines such as CXCR3 and CCR5, ligand chemokines (CXCL9, CXCL10, and CCL5) and other chemokines (CX3CL1 and CCL2)
- Adhesion molecules (MADCAM1, ICAM1, and VCAM1)
- Immune suppressive or counter regulatory genes like IDO1, PDCD1, PDL1, CTLA4 and FOXP3[3][4]
In several cancers these genes show great correlation,[3][4] a high expression of these genese indicates an active immune engagement and, at least a partial rejection of the cancer tissue. This phenotype is associated with a better prognosis and thus longer survival time.[4][3][2] In breast cancer the increased survival time observed in patiens displaying a high level of ICR gene expression was found to be associated with increased level of mutation of the tumor tissue while the poor immune pheneotype was defined by perturbation in the MAPK signalling pathways.[5]
References
- ^ Wang, Ena; Worschech, Andrea; Marincola, Francesco M. "The immunologic constant of rejection". Trends in Immunology. 29 (6): 256–262. doi:10.1016/j.it.2008.03.002.
- ^ a b Galon, Jérôme; Angell, Helen K.; Bedognetti, Davide; Marincola, Francesco M. "The Continuum of Cancer Immunosurveillance: Prognostic, Predictive, and Mechanistic Signatures". Immunity. 39 (1): 11–26. doi:10.1016/j.immuni.2013.07.008.
- ^ a b c Bedognetti, Davide; Hendrickx, Wouter; Marincola, Francesco M.; Miller, Lance D. "Prognostic and predictive immune gene signatures in breast cancer". Current Opinion in Oncology. 27 (6): 433–444. doi:10.1097/cco.0000000000000234.
- ^ a b c Bedognetti, Davide; Hendrickx, Wouter; Ceccarelli, Michele; Miller, Lance D; Seliger, Barbara. "Disentangling the relationship between tumor genetic programs and immune responsiveness". Current Opinion in Immunology. 39: 150–158. doi:10.1016/j.coi.2016.02.001.
- ^ Hendrickx, Wouter; Simeone, Ines; Anjum, Samreen; Mokrab, Younes; Bertucci, François; Finetti, Pascal; Curigliano, Giuseppe; Seliger, Barbara; Cerulo, Luigi (2017-02-06). "Identification of genetic determinants of breast cancer immune phenotypes by integrative genome-scale analysis". OncoImmunology. 0 (0): e1253654. doi:10.1080/2162402X.2016.1253654. ISSN 2162-402X. PMC 5353940.