Case Report: In Situ Vaccination by Autologous CD16+ Dendritic Cells and Anti-PD-L 1 Antibody Synergized With Radiotherapy To Boost T Cells-Mediated Antitumor Efficacy In A Psoriatic Patient With Cutaneous Squamous Cell Carcinoma
Authors: Jun-Wei Huang, Chun-Lin Kuo, Li-Tzu Wang, Kevin Sheng-Kai Ma, Wen-Yen Huang, Feng-Cheng Liu, Kuender D Yang, Bing-Heng Yang
Journal: Front Immunol (2021)
Keywords: checkpoint inhibitor combination therapy, cutaneous squamous cell carcinoma (cscc), dendritic cell-based immunotherapy, in situ vaccination, intratumoral injection therapy, monocyte-derived dendritic cells (modcs), psoriasis vulgaris (pv), radiotherapy
MeSH terms: B7-H1 Antigen / immunology, Cancer Vaccines / therapeutic use, Carcinoma, Squamous Cell / therapy, Dendritic Cells / transplantation, Immune Checkpoint Inhibitors / therapeutic use, Psoriasis / complications, Skin Neoplasms / therapy, Case Reports, Research Support, Non-U.S. Gov't, Adrenal Cortex Hormones / pharmacokinetics, Adrenal Cortex Hormones / therapeutic use, Aneurysm, False / etiology, Aneurysm, False / surgery, Angioplasty, Cancer Vaccines / administration & dosage, Carcinoma, Squamous Cell / complications, Carcinoma, Squamous Cell / drug therapy, Carcinoma, Squamous Cell / radiotherapy, Combined Modality Therapy, Dendritic Cells / chemistry, Dendritic Cells / immunology, Drug Interactions, GPI-Linked Proteins / analysis, Humans, Immune Checkpoint Inhibitors / administration & dosage, Immune Checkpoint Inhibitors / pharmacokinetics, Immunosuppressive Agents / pharmacokinetics, Immunosuppressive Agents / therapeutic use, Injections, Intralesional, Liver Cirrhosis / complications, Lymphocyte Activation, Lymphocytes, Tumor-Infiltrating / immunology, Male, Middle Aged, Psoriasis / drug therapy, Receptors, IgG / analysis, Skin Neoplasms / complications, Skin Neoplasms / drug therapy, Skin Neoplasms / radiotherapy, Tumor Burden, Wound Healing, Adrenal Cortex Hormones, B7-H1 Antigen, CD274 protein, human, Cancer Vaccines, FCGR3B protein, human, GPI-Linked Proteins, Immune Checkpoint Inhibitors, Immunosuppressive Agents, Receptors, IgG

The combination of radiotherapy and immunotherapy improves the survival rate of patients with malignancies developed through escape from T-cell-mediated immune surveillance. Immune checkpoint inhibitors, such as anti-programmed cell death protein-ligand 1 (anti-PD-L1) antibody, are used to rescue exhausted T cells. Simultaneously, dendritic cells (DCs) which are antigen-presenting cells that can initiate T-cell activation, are used to induce a tumor-specific immune response. However, the synergistic antitumor efficacy of the aforementioned combinational immunotherapy with intratumoral injection of low-dose DCs has not been reported, and the underlying therapeutic mechanism requires further investigation. Herein, we present the special case of a psoriatic patient with cutaneous squamous cell carcinoma (cSCC) in the right inguinal region, these two diseases characterized by opposing contradiction, further complicating treatments and side-effect management efforts. To treat the intractable SCC without exaggerating psoriasis, we developed the triple-regimen therapy (TRT) with the intratumoral injection of low-dose autologous DCs and anti-PD-L1 combined with radiotherapy. The injected DCs were obtained simply through leukapheresis without prior G-CSF administration for mobilization nor tumor-antigen loading for expansion. The patient received three radiation doses (24, 18, and 18 Gy) combined with three intratumoral injections of anti-PD-L1 antibody (40, 60, and 120 mg) plus autologous DCs (80% of the DC subpopulation being CD16+ myeloid DC with approximate amounts of 7.3 × 104, 2.5 × 106, and 1.7 × 107) within 10 weeks. The efficacy of the TRT was encouraging in shrinking tumor mass with remarkable SUVmax reduction (approximately 42%) on FDG PET-Scan despite relatively low-dose DCs were available. The low-dose intratumoral immunotherapy induced mild cutaneous side effects as expected. The transcriptomes were compared between pre-TRT and post-TRT biopsies to analyze underlying mechanical pathways of the TRT protocol. Over 10 highly significantly enriched T-cell-related pathways (P <0.0001) were identified in post-TRT biopsies. In addition, the activation of both innate and adaptive immunity was significantly enriched in post-TRT peripheral blood samples. We develop the easily accessible TRT which produces both local anti-tumor T-cell responses and systemic antitumor immunity for treating cSCC patients, especially for those with autoimmune disease.