Laser Immunotherapy: A Potential Treatment Modality for Keratinocyte Carcinoma

Abstract

The role of the immune system in cancer growth is well recognized and the development of immunotherapy represents a breakthrough in cancer treatment. Recently, the use of systemic immunotherapy was extended to keratinocyte carcinoma (KC), specifically locally advanced and metastasizing basal and squamous cell carcinoma. However, since most KC lesions are non-aggressive, systemic treatment with associated side effects is rarely justified. Conversely, topical immunotherapy with imiquimod remains restricted to premalignant and superficial lesions. Use of laser in the treatment of KC has evolved from physical tumor destruction and laser-assisted drug delivery to laser-mediated immune modulation. Evidence indicates that laser monotherapy can lead to immune cell infiltration, tumor reduction and resistance to tumor re-inoculation. Combining laser with immunotherapeutic agents, termed laser immunotherapy (LIT), may further potentiate immune activation and tumor response. Studies on LIT show not only direct anti-tumor effects but systemic adaptive immunity, illustrated by the prevention of tumor recurrence and regression in distant untreated tumors. These findings imply a therapeutic potential for both local and metastatic disease. This work provides rationales for immune-based treatment of KC and presents the current status of KC immunotherapy. Aiming to expand the field of KC immunotherapy, the review discusses the literature on immune activation following laser monotherapy and LIT.

Anti-PD-1 Therapy with Adjuvant Ablative Fractional Laser Improves Anti-Tumor Response in Basal Cell Carcinomas

“…AFL exposure, partially due to the thermal injury to skin cells, stimulates a substantial anti-tumor immune response, including recruitment of neutrophils and antigen-specific cytotoxic T-cells [ 10 , 19 , 20 ]. This process involves the induction of immunogenic cell death followed by the release of damage-associated molecular patterns (DAMPs) and potential neoantigens, resulting in the activation of innate and adaptive immune cells [ 21 , 22 , 23 , 24 , 25 ]. In accordance with this, AFL has been shown to stimulate the local infiltration of immune cells in healthy human skin by increasing the levels of immune-attracting cytokines and growth factors, including IL-6, transforming growth factor-β, basic fibroblast growth factor, and platelet-derived growth factor [ 26 , 27 ].…”

Anti‐PD‐1 immunotherapy with adjuvant ablative fractional laser displays increased tumour clearance of squamous cell carcinoma, a murine study

“…The use of adjuvant AFL for cancer treatment is being explored in both preclinical and clinical studies. 35 AFL has been explored successfully in several clinical studies treating actinic keratosis and BCCs including a very recent study that investigated intratumoural administration of anti-PD-1 with adjuvant AFL. 23,[36][37][38][39] Further, few case studies have investigated laser immunotherapy for malignant melanoma and refractory SCC using near-infrared lasers.…”

Finite Element Method (FEM) Modeling of Laser-Tissue Interaction during Hair Removal

“…However, our model can be easily adapted to incorporate shorter pulses. Another potential extension of our FEM modeling approach would be to simulate laser treatment of keratinocyte carcinoma [43].…”