Fig. 6.

Potential Multiple Factors Determine the Quality of Immunological Synapse in Cancer immunotherapy. The development of a novel SPE approach to predict the effectiveness of Chimeric Antigen Receptor (CAR)-modified cells by quantifying the quality of immunological synapse is dependent on multiple factors. In addition to patient conditions (e.g., age, sex, tumor burden, stage of diseases, tumor antigen mutations & loss, etc.), there are three main aspects to be considered to quantify the quality IS. First, intrinsic potency of CAR-modified immune cells includes different subsets of CAR-modified immune cells, different modifications of CAR constructs, inhibitory receptor expression, and CAR tonic signaling. Second, intra-tumor heterogeneity (IHT) includes mutations of tumors, inhibitory ligand (e.g., PD-L1) expression, suppressor cells, and tumor stiffness. Third, tumor microenvironment (TME) contains cytokine milieu, metabolites, hypoxia, and collagen fibers around tumor cells