Spatially mapping the immune landscape of melanoma using imaging mass cytometry.

Melanoma is an immunogenic cancer with a high response rate to immune checkpoint inhibitors (ICIs). It harbors a high mutation burden compared with other cancers and, as a result, has abundant tumor-infiltrating lymphocytes (TILs) within its microenvironment. However, understanding the complex interplay between the stroma, tumor cells, and distinct TIL subsets remains a substantial challenge in immune oncology. To properly study this interplay, quantifying spatial relationships of multiple cell types within the tumor microenvironment is crucial. To address this, we used cytometry time-of-flight (CyTOF) imaging mass cytometry (IMC) to simultaneously quantify the expression of 35 protein markers, characterizing the microenvironment of 5 benign nevi and 67 melanomas. We profiled more than 220,000 individual cells to identify melanoma, lymphocyte subsets, macrophage/monocyte, and stromal cell populations, allowing for in-depth spatial quantification of the melanoma microenvironment. We found that within pretreatment melanomas, the abundance of proliferating antigen-experienced cytotoxic T cells (CD8+CD45RO+Ki67+) and the proximity of antigen-experienced cytotoxic T cells to melanoma cells were associated with positive response to ICIs. Our study highlights the potential of multiplexed single-cell technology to quantify spatial cell-cell interactions within the tumor microenvironment to understand immune therapy responses.

Maternal risk factors for adverse outcome in asphyxiated newborns treated with hypothermia: parity and labor duration matter.

INTRODUCTION: Perinatal asphyxia remains a frequent cause of neonatal mortality and long-term neurodevelopmental sequelae, despite the introduction of therapeutic hypothermia. Specific maternal characteristics may predispose asphyxiated newborns treated with hypothermia to worse outcome. OBJECTIVE: To investigate the possible association between specific maternal factors and adverse outcome in asphyxiated newborns treated with hypothermia. METHODS: We conducted a retrospective review of our database of 215 asphyxiated newborns treated with hypothermia from 2008 to 2015. We collected maternal characteristics including parity and labor duration, and we defined adverse outcome as death and/or brain injury. We compared the maternal characteristics between the asphyxiated newborns who developed adverse outcome and those who did not. RESULTS: Asphyxiated newborns born to nulliparous mothers had a significantly higher risk of adverse outcome (61%), compared to asphyxiated newborns born from primiparous (19%) and multiparous (20%) mothers (p = .002). Labor duration was longer in nulliparous mothers (p = .04). Among mothers who delivered vaginally, labor duration was significantly longer in newborns developing adverse outcome (p = .04). In multivariable analysis, parity was confirmed as an independent predictor of adverse outcome in all newborns, but labor duration showed a borderline non-significant association with adverse outcome (p = .051) only in newborns born vaginally. Labor duration beyond 12 h of life was associated with maximal sensitivity and specificity in detecting asphyxiated newborns at an increased risk of adverse outcome despite hypothermia treatment (AUC 0.62, p = .044). CONCLUSIONS: Newborns with evidence of perinatal asphyxia, born to nulliparous mothers, and especially to those in whom the duration of labor has been prolonged, might be at higher risk of death or brain injury despite the use of therapeutic hypothermia.