Melanoma is one of the deadliest
malignancies with a high risk of relapse and
metastasis. Long-term,
tumor-specific, and systemic immunity induced by local intervention is ideal for personalized
cancer therapy.
Laser immunotherapy (LIT), a combination of local irradiation of
laser and local administration of an
immunostimulant, was developed to achieve such an immunity. Although LIT showed promising efficacy on
tumors, its immunological mechanism is still not understood, especially its spatio-temporal dynamics. Methods: In this study, we investigated LIT-induced immunological responses using a 980-nm
laser and a novel
immunostimulant,
N-dihydrogalactochitosan (GC). Then we followed the functions of key immune cells spatially and temporally using intravital imaging and immunological assays. Results: Immediately after LIT, GC induced a rapid infiltration of neutrophils which ingested most GC in
tumors. The
cytokines released to the serum peaked at 12 h after LIT.
Laser irradiations produced photothermal effects to ablate the
tumor, release damage-associated molecular patterns, and generate whole-cell
tumor vaccines. LIT-treated
tumor-bearing mice efficiently resisted the rechallenged
tumor and prevented lung
metastasis. Intravital imaging of
tumor at rechallenging sites in LIT-treated mice revealed that the infiltration of tumor-infiltrating lymphocytes (TILs) increased with highly active motility. Half of TILs with arrest and confined movements indicated that they had long-time interactions with
tumor cells. Furthermore, LIT has synergistic effect with checkpoint blockade to improve antitumor efficacy. Conclusion: Our research revealed the important role of LIT-induced neutrophil infiltration on the in situ whole-cell
vaccine-elicited antitumor immune response and long-term T cell immune memory.