Abstract B20: Fractional laser exposure can stimulate systemic anti-tumor immune response
Authors: Kawakubo Masayoshi , Manstein Dieter 
Published: March 2017

Background: 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 procedure and burns. In this study we explore the utility of aFP for treating oncological indications, including induction of local tumor regression or inducing anti-tumor immunity which is in marked contrast to current indications of aFP.

Methodology/Principal Findings: Six-week-old female BALB/c mice were inoculated intradermally on the left leg with murine colon carcinoma cell line (CT26.CL25) which expressed a tumor antigen, beta-galactosidase (beta-gal). At day eight, when tumors reached a diameter of approximately 5–7 mm, the tumor site was irradiated with a fractional CO2 laser (100 mJ pulse energy, 5% laser density (surface coverage), 300 Hz pulse frequency). Tumor-free mice after FP treatment for 90 days were rechallenged with CT26.CL25 tumor cells on the opposite leg. To determine the mechanism of this tumor protection BALB/c Nu/Nu mice lacking lymphocytes mediated immunity were subjected to the same protocol. FP treated tumors grew significantly slower as compared to untreated controls (p&lt;0.005). Complete remission after a single FP treatment was observed in 6 of 13 CT26.CL25 tumor-bearing mice (47%) in treated group, but one of 13 mice in the control group (p&lt;0.05). All 6 mice survived for an additional 60 days with no detectable tumors after rechallenge test. The FP-treated group using BALB/c Nu/Nu nude mice showed a delay in tumor growth. But tumors then grew progressively, as in the control group, suggesting a requirement for lymphocyte-mediated adaptive immunity for long term tumor eradication. Flow cytometric analysis of the FP-treated tumors showed less infiltrating regulatory T lymphocytes in the tumor at 7 day after FP treatment in CT26.CL25 tumor-bearing mice. CD8 T lymphocytes from drainage lymph node of survival mice in treated group showed more cytotoxicity than control group. Adoptive transfer experiment using CD8 T lymphocytes from drainage lymph node of survival mice in treated group to BALB/c Nu/Nu nude mice showed a delay in tumor growth comparing with control group.

Conclusion: We have demonstrated that ablative fractional photothermolysis is able to induce systemic anti-tumor adaptive immunity preventing tumor recurrence in a murine colon carcinoma in a mouse model. This study has demonstrated a potential role of FP treatments in oncology and further studies should be performed. Although FP treatments of oncological applications hold promise and should further be investigated, at present time FP is not be performed as clinical care for tumors.

Citation Format: Masayoshi Kawakubo, Dieter Manstein. Fractional laser exposure can stimulate systemic anti-tumor immune response. [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer: From Initiation to Outcomes; 2016 Sep 17-20; Tampa, FL. Philadelphia (PA): AACR; Cancer Res 2017;77(3 Suppl):Abstract nr B20.