The poor response of pancreatic ductal adenocarcinoma (PDAC) to treatment, including immunotherapy, is attributed to its tumor microenvironment (TME). An ongoing challenge is the desmoplastic and immunosuppressed TME that evades immune surveillance. Here, we investigate transient modulation of the TME to overcome immunosuppression using a light-activated process, termed photodynamic priming (PDP). As a first step, this study captures the temporal dynamics of variations in immune infiltrates and subsequent immune responses in the TME, spleen, and blood of the KPC mouse model of PDAC post-PDP. In response to PDP, there were transient increases in tumor infiltrating lymphocytes (TIL) in tumors. The TIL population post-PDP includes an enrichment of CD8