Case Report: Combined Intra-Lesional IL-2 and Topical Imiquimod Safely and Effectively Clears Multi-Focal, High Grade Cutaneous Squamous Cell Cancer in a Combined Liver and Kidney Transplant Patient

Abstract

Cutaneous squamous cell carcinoma (cSCC) is the second most common non-melanoma skin cancer worldwide, with ever increasing incidence and mortality. While most patients can be treated successfully with surgical excision, cryotherapy, or radiation therapy, there exist a subset of patients with aggressive cSCC who lack adequate therapies. Among these patients are solid organ transplant recipients who due to their immunosuppression, develop cSCC at a dramatically increased rate compared to the normal population. The enhanced ability of the tumor to effectively undergo immune escape in these patients leads to more aggressive tumors with a propensity to recur and metastasize. Herein, we present a case of aggressive, multi-focal cSCC in a double organ transplant recipient to frame our discussion and current understanding of the immunobiology of cSCC. We consider factors that contribute to the significantly increased incidence of cSCC in the context of immunosuppression in this patient population. Finally, we briefly review current literature describing experience with localized therapies for cSCC and present a strong argument and rationale for consideration of an IL-2 based intra-lesional treatment strategy for cSCC, particularly in this immunosuppressed patient population.

Intralesional Treatments for Invasive Cutaneous Squamous Cell Carcinoma

“…It has been used in advanced clear cell renal carcinoma and melanoma but its severe cardiovascular, respiratory, and infectious complications have limited its use. Combined intralesional IL-2 (8–10 MUI per session, weekly) and topical imiquimod have been used in a multifocal high-grade cSCC on the face occurring in a double-transplant patient (kidney and liver) with complete tumor clearance after 3 months of follow-up and no repercussions in liver or kidney function [ 94 ].…”

Cutaneous Breast Cancer Metastasis Is Effectively Treated With Intralesional Interleukin-2 and Imiquimod: A Case Report and Brief Literature Review

“…At her third IL-2 treatment, physical exam revealed the chest wall nodule was now slightly more prominent, suggesting partial response to IL-2: thus, imiquimod cream was added to the biweekly IL-2 injections with the aim to promote and maintain a stronger anti-tumor immune response. Imiquimod is a TLR7 agonist and immunoadjuvant that has been used successfully for the treatment of in-transit melanoma and squamous cell carcinoma ( 11 ), and with which we have also had some success in treating primary cutaneous malignancies. It is dosed as daily topical application to the affected area for a total of five days, starting on the day of IL-2 injection.…”

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

“…Therefore, combing cemiplimab with other treatments that could potentially boost its immune modulating effect may enhance the antitumor response 13 . Locally applied immune modulators could be considered such as imiquimod or ablative fractional laser (AFL) 14–16 . In recent preclinical studies, AFL have been explored as an adjuvant treating various cancer models 15–19 .…”

“…13 Locally applied immune modulators could be considered such as imiquimod or ablative fractional laser (AFL). [14][15][16] In recent preclinical studies, AFL have been explored as an adjuvant treating various cancer models. [15][16][17][18][19] AFL treatment itself induced an antitumor effect as well as immune response by recruiting neutrophils and T cells.…”