001, pn(F) < 0.001, Figure Figure4A).4A). However, no difference was observed between samples of unaffected colon and carcinoma tissue (paired, pCD = 0.471, pn(F) = 0.2783, Figure Figure4C4C). Figure 4 Statistical comparison of repertoire restriction degree measured in Vandetanib FDA CD and n(F). Compared were samples from blood with tissue (both normal colon and carcinoma, A), blood from healthy controls with blood from carcinoma patients (B), and tumor free colon … Comparison of elevated families in different compartments For 16 patients, samples of tumor and tumor free colon were available. In the carcinoma samples, altogether 30 families were elevated (0-5 families per patient). In the corresponding samples of unaffected colon tissue, 14 families were elevated (0-4 families per patient).

In only two of these patients a single family was elevated in both tumor tissue and corresponding unaffected colon. For nine CRC patients, blood and tumor samples were available. Four of these patients had elevated families in peripheral blood, but none of these families was elevated in the corresponding tumor sample. Please refer to figure figure44. Discussion In this study, TCR V��-family repertoire restrictions in blood and tissue of patients with colorectal carcinoma were compared using high throughput relative quantification of TCR V��-families based on qRT PCR technology. While a multitude of mathematical approaches have been established to describe the degree of repertoire restriction in single V-families from spectratype/immunoscope data (reviewed in [45]), to our knowledge, a model to describe global TCR repertoire restriction based on V-family quantification has not been published so far.

Colorectal carcinoma is thought to be of limited immunogenicity. Nevertheless, global V��-repertoire restriction degree in blood reflected by the CD and n(F) values was significantly higher in carcinoma patients confirming the results of former studies investigating V��-repertoire restrictions in blood of patients with other tumor entities, which have been interpreted as indication for the induction of specific clones reactive to autologous tumor [26,42]. In fact, this TCR repertoire restriction in tumor patients might be attributed to cumulative V��-alterations caused by discrete epitope-specific T-cell expansions triggered by several Batimastat different antigens. Because of the epitope-independency of the assay, unspecific antigen confrontation due to barrier disruption as postulated in the context of other tumor entities [28,32] causing additional repertoire alterations can not be excluded.