CCL21 and cancer: What remains to be clearly elucidated are (1) whether the tumor cell itself is responsible for expression, or lack thereof, of these critical factors or their upstream regulators (e.g., IRFs, STATs and NF-κB); (2) the immune deficits present in each individual cancer type that result after dysregulation of CCL19, CCL21, CXCL13 and LTαβ expression and/or signaling; and (3) how immunotherapy treatment either alone or in conjunction with current chemotherapy can be used to manipulate the tumor immune environment to re-activate an anti-tumor response.