Immune signatures of murine and human cancers reveal unique mechanisms of tumor escape and new targets for cancer immunotherapy.
OBJECTIVE
Despite lymphocyte infiltration of tumors and the activation of tumor-draining lymph nodes, malignant tumors are able to "escape" from both innate and adaptive immune responses. For immunotherapy to be successful, it must reverse these escape mechanisms, which necessitates explicit and tumor-specific elucidation of tumor escape strategies.


METHODS
To identify relevant escape mechanisms in murine tumors and in two corresponding human cancers, real-time reverse transcription-PCR was used to measure a panel of genes associated with T-cell activation and inhibition pathways.


RESULTS
Comparative analysis of the expression levels of these immunomodulatory genes showed astonishing similarities in expression patterns between murine and human breast cancers but profound variability in the expression of immunomodulatory genes in colorectal cancers. For human ductal adenocarcinoma of the breast, down-regulation of dendritic cell maturation marker CD83 and T-cell activation gene CD28 was observed as well as a notable increase in the expression of the immunoinhibitory gene B7-H4. By contrast, colorectal adenocarcinoma cases showed high variability in tumor escape mechanisms, indicating a need to produce immune signatures for individual patients to identify appropriate immunotherapeutic targets.


CONCLUSIONS
These results show that certain tumors, such as ductal carcinoma of the breast, show consistent immunologic abnormalities that can be used as targets for immunotherapy. These findings also show the importance and feasibility of determining the immune signatures of patients' tumors to select appropriate immunotherapeutic strategies. Ultimately, these results advocate for the determination of immune signatures as part of the customary repertoire of clinical diagnostics for cancer.
Sadun
Rebecca E
RE
Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA.
Sachsman
Suzanne M
SM
Chen
Xiaoying
X
Christenson
Kamilee W
KW
Morris
William Z
WZ
Hu
Peisheng
P
Epstein
Alan L
AL
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D018122:B7-1 Antigen / Q000096:biosynthesis; D018106:CD28 Antigens / Q000096:biosynthesis; D045744:Cell Line, Tumor; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D007167:Immunotherapy / Q000379:methods*; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000628:therapy*; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1; D000097802:CD83 Antigen
D015703:Antigens, CD; D018122:B7-1 Antigen; D018106:CD28 Antigens; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1; D000097802:CD83 Antigen; C475826:VTCN1 protein, human