461 Preclinical development of desmoglein chimeric autoantibody receptor (CAAR) T cells for pemphigus therapy

Abstract

One of the challenges in caring for patients with mycosis fungoides, the most common cutaneous T-cell lymphoma (CTCL), is early identification of patients who will develop progressive disease. While TNM staging is prognostic, identification of high-risk patients earlier in their disease remains an unmet clinical need. We hypothesized that the balance between anti-tumor CD8 + T cell and anti-inflammatory FOXP3 + T regulatory cell infiltration in the initial CTCL skin biopsy could be predictive of disease progression. To examine this, a cohort of 33 CTCL patients (9 I, 4 II) with a median follow-up of 78 months were divided into two groups depending on whether they developed progressive disease (n¼13). We studied their skin biopsy specimens by multiplexed tyramide signal amplification based staining for CD4, CD8, FoxP3, PD-1 and DAPI expression, followed by image deconvolution and automated cell analysis. Patients with greater CD8 + T cell infiltration had significantly improved progression-free survival in univariate (HR¼0.6, CI 0.4-0.97, p¼0.04) and multivariate analysis (HR 0.4, CI 0.2-0.7, p¼0.01). When we restricted the analysis to early stage patients, this finding remained significant (HR¼0.6, CI 0.4-0.98, p¼0.04) and did not correlate with malignant clone frequency or age. The number of FoxP3 + regulatory T cells, PD-1 + T cells and total CD4 + T cells were not associated with improved survival. Ratios between these cell types were also examined for potential associations with prognosis. We found that an increased ratio of CD4 + T cells:FoxP3 + T cells was associated with worse PFS (HR 1.02, CI 1.0-1.03, p¼.01) but this result did not remain significant in multivariate analysis (p¼0.7). We are in the process of confirming this finding in a larger cohort. In summary, CD8 + T cell density in the lesional skin of CTCL patients is predictive of disease progression and may be a useful adjunct in risk-stratifying early stage patients.