CORE--IMMUNOTHERAPY

Mayo Clinic Rochester, Rochester MN

Investigators

Linked publications, trials & patents

Abstract

The Immune Monitoring Facility was established to provide ancillary, immunological analyses in clinical protocols to evaluate the effects of immunotherapy on immunological functions that are believed to be important for the elimination of tumors. The offered services are principally directed toward (1) identifying lymphocyte populations and immunological functions that are altered by immunotherapy and (2) estimating the diversity of T cell receptor repertoires in cancer patients and the effects of treatment modalities on T cell receptor diversity. The analysis of tumor-specific immune responses focuses on cytotoxic T lymphocytes (CTL) due to their demonstrated abilities to lyse tumor cells and secrete cytokines. The two most important assays of tumor-specific CTL function involve the estimation of the frequencies of tumor-specific CTLs through (1) flow cytometric estimation of the frequencies of CTLs that bind HLA class I dimers/tetramers that include tumor-associated peptides and (2) the use of Elispot assays to estimate the frequencies of CTLs that secrete IFNgamma,or IL-5 in response to tumor-associated antigens/peptides. The diversity of T cell receptor (TcR) repertoire is evaluated through RT-PCR-based spectratyping of alpha and beta transcripts expressed by CD4 + and CD8 + T cells. The inclusion of analyses of TCR repertoire exemplifies the philosophy that has driven the evolution of this facility. Historically, monitoring facilities have focused on identifying shifts in specific immune functions that are related to immunotherapy. We have taken the view that understanding the importance of these therapy-related changes requires an evaluation of the immune potentials of cancer patients prior to treatment. Accordingly, it is essential to understand the relationship between immunological responses of patients and those of appropriately matched, healthy humans. Further, tumor-specific immune responses must be evaluated in relation to the adaptation of tumors to effective immune responses since the interplay between these two dynamic forces expectedly comprises an important factor in determining clinical outcome. Therefore, the Immune Monitoring Facility plays a central role in evaluating tumor-specific immune responses, relating these responses to the immune potentials of patients relative to healthy individuals, and relating tumor-specific responses to the opposing forces of tumor immunoselection. Although this Facility is not directly involved in evaluating all of these aspects of tumor-specific immunity, i.e. immunoselection, it is intimately involved in developing the strategy for such comprehensive analyses.