CD8(+) T cell skin infiltration predicts disease progression in CTCL patients

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 (n=13). 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 (HR=0.6, CI 0.4-0.97, p=0.04) and multivariate analysis (HR 0.4, CI 0.2-0.7, p=0.01). When we restricted the analysis to early stage patients, this finding remained significant (HR=0.6, CI 0.4-0.98, p=0.04) 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, p=.01) but this result did not remain significant in multivariate analysis (p=0.7). 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.