Laser Immunotherapy: A Potential Treatment Modality for Keratinocyte Carcinoma

SIMPLE SUMMARY: In light of expanding incidences of keratinocyte carcinoma (KC) with many patients developing multiple tumors, the demand for new treatment modalities is high. With the approval of cemplimab for locally advanced and metastasizing basal cell carcinoma and squamous cell carcinoma, KC is now included as an indication for systemic immunotherapy. At present, however, systemic KC therapy remains limited by the severe side effects associated with treatment. Immunotherapy might be more broadly applied if locally administered. Localized to the skin, KCs are easily accessible to topical drugs and physical interventions such as laser. There is an increasing appreciation of lasers’ potential to activate an immune response. Further enhancement of the laser-based immune activation might be obtained by combining laser and immunotherapeutic agents, known as laser immunotherapy. In search of new treatment modalities for KC and aiming to broaden the field of KC immunotherapy, this review discusses the current literature on immune activation following both laser monotherapy and laser immunotherapy. 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.