Fractional laser exposure induces neutrophil infiltration (N1 phenotype) into the tumor and stimulates systemic anti-tumor immune response

• Published in: PloS one Vol. 12; no. 9; p. e0184852
• Main Authors: Kawakubo, Masayoshi, Demehri, Shadmehr, Manstein, Dieter
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 18.09.2017; Public Library of Science (PLoS)
• Subjects: Ablation; Acne; Adaptive immunity; Analysis; Animals; Bioavailability; Biology; Biology and Life Sciences; Cancer therapies; Carbon dioxide; Carbon dioxide lasers; Care and treatment; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Cell Line, Tumor; Cell survival; Colon; Colonic Neoplasms - immunology; Colonic Neoplasms - radiotherapy; Colorectal cancer; Dermatology; Drug delivery; Drug delivery systems; Engineering and Technology; Epitopes; Female; Flow cytometry; Galactosidase; Growth factors; Hospitals; Immune response; Immune system; Immunity; Immunity, Cellular; Infiltration; Inoculation; Irradiation; Lasers; Lesions; Low-Level Light Therapy - methods; Lymphocytes; Lymphocytes T; Medical lasers; Medicine and Health Sciences; Metastases; Metastasis; Mice; Mice, Inbred BALB C; Neutrophil Infiltration; Neutrophils; Neutrophils - immunology; Photodynamic therapy; Physiological aspects; Regression analysis; Remission; Research and Analysis Methods; Scars; Skin; Skin cancer; Studies; Surgery; Survival; T-Lymphocytes, Regulatory - metabolism; Tumor-infiltrating lymphocytes; Tumors; β-Galactosidase; United States; United States > US; Massachusetts
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0184852

Ablative fractional photothermolysis (aFP) using a CO2 laser generates multiple small diameter tissue lesions within the irradiation field. aFP is commonly used for a wide variety of dermatological indications, including treatment of photodamaged skin and dyschromia, drug delivery and modification of scars due to acne, surgical procedures and burns. In this study we explore the utility of aFP for treating oncological indications, including induction of local tumor regression and inducing anti-tumor immunity, which is in marked contrast to current indications of aFP. We used a fractional CO2 laser to treat a tumor established by BALB/c colon carcinoma cell line (CT26.CL25), which expressed a tumor antigen, beta-galactosidase (beta-gal). aFP treated tumors grew significantly slower as compared to untreated controls. Complete remission after a single aFP treatment was observed in 47% of the mice. All survival mice from the tumor inoculation rejected re-inoculation of the CT26.CL25 colon carcinoma cells and moreover 80% of the survival mice rejected CT26 wild type colon carcinoma cells, which are parental cells of CT26.CL25 cells. Histologic section of the FP-treated tumors showed infiltrating neutrophil in the tumor early after aFP treatment. Flow cytometric analysis of tumor-infiltrating lymphocytes showed aFP treatment abrogated the increase in regulatory T lymphocyte (Treg), which suppresses anti-tumor immunity and elicited the expansion of epitope-specific CD8+ T lymphocytes, which were required to mediate the tumor-suppressing effect of aFP. We have demonstrated that aFP is able to induce a systemic anti-tumor adaptive immunity preventing tumor recurrence in a murine colon carcinoma in a mouse model. This study demonstrates a potential role of aFP treatments in oncology and further studies should be performed.