Abstract
Recent technical improvements in evaluations of immune cells in situ and immune monitoring of patients with cancer have provided a wealth of new data confirming that immune cells play a key role in human cancer progression. This, in turn, has revived the expectation that immune endpoints might serve as reliable biomarkers of outcome or response to therapy in cancer. The recent successes in linking the T-cell signature in human colorectal carcinoma (CRC) with prognosis have provided a strong motive for searching for additional immune biomarkers that could serve as intermediate endpoints of response to therapy and outcome in human cancers. A number of potentially promising immune biomarkers have emerged, but most remain to be validated. Among them, the B-cell signature, as exemplified by expression of the immunoglobulin G kappa chain (IGKC) in tumor-infiltrating lymphocytes (TIL), has been validated as a biomarker of response to adjuvant therapy and better survival in patients with breast carcinoma and several other types of human solid tumors. Additional immune endpoints are being currently tested as potentially promising biomarkers in cancer. In view of currently growing use of immune cancer therapies, the search for immune biomarkers of prognosis are critically important for identifying patients who would benefit the most from adjuvant immunotherapy.
Highlights
It has been well established that the development of cancer is associated with alterations in numbers and functions of immune cells in the peripheral circulation and especially at the sites of tumor progression
This difficulty in establishing meaningful correlations of immune with clinical endpoints has been variously attributed to the complexity of interactions between the host immune system and the tumor, an inadequate quality of immune monitoring used to measure these interactions and/or a failure to measure those aspects of immune responses that are most relevant to cancer progression
It is likely that the characteristics of tumor cells influence the potential of immune responses to serve as useful biomarkers of prognosis
Summary
It has been well established that the development of cancer is associated with alterations in numbers and functions of immune cells in the peripheral circulation and especially at the sites of tumor progression. We have reported spontaneous apoptosis of circulating CD8+ antigen-responding effector T cells, leading to rapid lymphocyte turnover and depressed absolute numbers of T cell subsets in cancer patients tested prior to oncologic therapies (Whiteside, 2005) Together, these data identifying the high pretreatment NLR as a significant independent predictor of poor cancer-specific survival provide a strong rationale for considering a rapid validation of this promising biomarker. Even prospective monitoring for cytokines may be biased by the fact that current antibody-based assays measure soluble mediators, while those tethered to membranes of microvesicles present in body fluids remain undetected, as recently reported (Szczepanski et al, 2011) For this reason, the usefulness of cytokine/chemokine profiles as surrogate biomarkers of cancer progression remain limited and further studies linking these profiles with clinical outcomes are in order. The potential value of TEX as biomarkers of the tumor fate during and after therapy can be confirmed in future prospective studies
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
