When results of T cell immune monitoring match/do not match clinical outcomes of tumor vaccine trials: What more could and should we measure?

Abstract

Activation of cancer-specific T cells by tumor vaccines can lead to the rejection of the tumor. However, monitoring the tumor-specific T cell response continues to be a challenge. The magnitude and cytokine effector lineage of the vaccine-induced T cells, their ability to kill, and the avidity of the T cells for the tumor are among the primary parameters that define the T cell's potential impact on the tumor. Due to determinant spreading, immunization with a tumor antigen can result in recruitment of T cells with specificity for unrelated antigens of the tumor. The efficacy of this second wave T cell repertoire will depend on clonal sizes, effector lineages, and their avidities for the tumor. Comprehensive immune monitoring should be able to measure all the above parameters of the primary and secondary T cell responses to the tumor. In this chapter, we propose an ELISPOT-based protocol which can help accomplish the above goal with reasonable cost and effort, requiring only 10 ml of patient blood.