These barriers include: i) chemokine/receptor mismatch between the CAR T cell chemokine receptors and the chemokines secreted by tumors (e.g. such as CXCL1, CXCL5 and CXCL12), ii) low levels of tumor-derived chemokines for which effector CAR T cells lack receptors, iii) abnormal tumor vascularity and iv) physical (e.g. extracellular matrix (ECM]) and cellular barriers (e.g. cancer associated-fibroblasts [CAFs]) (80, 81). Here, CXCL12 is linked to neoplasm.