Immune biomarkers are more accurate in prediction of survival in ulcerated than in non-ulcerated primary melanomas

Abstract

Introduction Ulcerated melanomas may have a unique biology and microenvironment. We test whether markers of immune infiltration correlate with clinical outcome in ulcerated compared to non-ulcerated primary melanoma tumors. Methods Sixty-two stage II–III cutaneous melanomas, 32 ulcerated and 30 non-ulcerated, were analyzed for tumor-infiltrating lymphocytes (TILs). Immunohistochemistry (IHC) was performed for CD2, a marker previously shown to correlate with overall survival (OS) and recurrence-free survival (RFS) in this patient population. IHC using antibody, VE1, to BRAF V600E was also performed on a subset of 41 tumors to assess the relationship of BRAF mutation to immune markers. Results We found, using Cox regression models, that the presence of TILs was associated with improved OS (p = 0.034) and RFS (p = 0.002) in ulcerated melanoma tumors, but not in non-ulcerated melanoma (p = 0.632, 0.416). CD2 expression also was correlated with improved OS (p = 0.021) and RFS (p = 0.001) in ulcerated melanoma, but no relationship was seen in non-ulcerated melanoma (p = 0.427, 0.682). In this small population, BRAF status did not correlate with TILs or CD2+ count. Conclusion Our data show that immune markers including TILs and CD2 count correlate more closely with survival in ulcerated melanomas than that in non-ulcerated melanomas. We propose that immune biomarkers may be particularly relevant to ulcerated, as compared to non-ulcerated, melanomas and that this merits study in larger populations.

T-cell Landscape in a Primary Melanoma Predicts the Survival of Patients with Metastatic Disease after Their Treatment with Dendritic Cell Vaccines

“…So far, most groups studying the correlation between TILs and patient survival classify the presence of TILs as absent, nonbrisk and brisk (11,15,16). Some characterize TILs only as present or absent (44), while few use a more elaborate method that takes both the distribution and the density of TILs into account (12). Our method also takes distribution and density into account and does this in an automated and quantitative manner using the entire tumor slide.…”

Risk factors for recurrence of malignant melanoma in patients with negative sentinel lymph node biopsy

“…Since both NM and ALM are associated with lower levels of tumor infiltrating lymphocytes, which are known to correlate with poor outcomes in melanoma, it is possible that differences in the immunogenicity of the primary melanoma are relevant for recurrence after negative SLNB [13,14]. Similarly, changes in the tumor microenvironment in ulcerated melanoma might explain why ulceration is associated with overall recurrence in patients with negative SLNs, since ulcerated melanoma may interact differently with the immune system [15]. To our knowledge, our study is the first to identify ulceration as a risk factor for hematogenous spread.…”

The avidity of tumor‐specific T cells amplified by a plasmacytoid dendritic cell‐based assay can predict the clinical evolution of melanoma patients

“…This is reinforced by the effectiveness of immunotherapies based on immune checkpoint blockers that allow for reversal of melanoma-induced immunosuppression correlated with the presence of neoantigens expressed by the tumor (McGranahan et al, 2016;Van Allen et al, 2015). Consistent with this hypothesis, some studies suggested that the presence, number, or quality of T lymphocyte infiltrates, specifically CD8 + T cells, is an independent and favorable prognostic factor in melanoma (Erdag et al, 2012;Jacquelot et al, 2016;de Moll et al, 2015;Piras et al, 2005). Ongoing investigations are analyzing the host immune response against cancer to evaluate the prognostic impact of in situ immune-cell infiltrates in tumors and defined as an "immunoscore" (Galon et al, 2012).…”