Tumor infiltrating lymphocytes in acral lentiginous melanoma: a study of a large cohort of cases from Latin America

Castañeda, Carlos A.; Torres‐Cabala, Carlos A.; Castillo, Miluska; Villegas, Valeria; Casavilca, Sandro; Cano, Luis; Sanchez, Joselyn; Dunstan, Jorge; Calderón, Gabriela; Cruz, Miguel De la; Cotrina, José M.; Gómez, Henry; Galvez, Renato; Abugattas, Julio

doi:10.1007/s12094-017-1685-3

Cited by 46 publications

(35 citation statements)

References 59 publications

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“…This is in accordance with the research conducted by Castaneda et al . [ 16 ] In that study, it was stated that TILs in acral MM were fewer in number compared to in other MM types and this corresponded to the depth of invasion, progression rate and survival rate.…”

Section: Discussionmentioning

confidence: 99%

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The Major Role of NF-κB in the Depth of Invasion on Acral Melanoma by Decreasing CD8+ T Cells

Usman

Hernowo

Tobing

et al. 2018

J Pathol Transl Med

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BackgroundThe tumor microenvironment including immune surveillance affects malignant melanoma (MM) behavior. Nuclear factor κB (NF-κB) stimulates the transcription of various genes in the nucleus and plays a role in the inflammatory process and in tumorigenesis. CD8+ T cells have cytotoxic properties important in the elimination of tumors. However, inhibitory receptors on the cell surface will bind to programmed death-ligand 1 (PD-L1), causing CD8+ T cells to lose their ability to initiate an immune response. This study analyzed the association of NF-κB and PD-L1 expression levels and CD8+ T-cell counts with depth of invasion of acral MM, which may be a predictor of aggressiveness related to an increased risk of metastasis.MethodsA retrospective cross-sectional study was conducted in the Department of Anatomical Pathology, Faculty of Medicine, Universitas Padjadjaran/Hasan Sadikin Hospital using 96 cases of acral melanoma. Immunohistochemical staining was performed on paraffin blocks using anti–NF-κB, –PD-L1, and -CD8 antibodies and invasion depth was measured using dotSlide-imaging software.ResultsThe study showed significant associations between the individual expression of NF-κB and PD-L1 and CD8+ T-cell number, with MM invasion depth. NF-κB was found to be a confounding variable of CD8+ T-cell number (p < .05), but not for PD-L1 expression (p = .154). Through multivariate analysis it was found that NF-κB had the greatest association with the depth of invasion (p < .001), whereas PD-L1 was unrelated to the depth of invasion because it depends on the number of CD8+ T cells (p = .870).ConclusionsNF-κB plays a major role in acral MM invasion, by decreasing the number of CD8+ T cells in acral MM.

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Section: Discussionmentioning

confidence: 99%

“…PD-L1 staining in membranes and in the cytoplasm was assessed on a semi-quantitative scale: positive when stained area was ≥ 5% and negative when < 5% ( Fig. 2 ) [ 16 ]. The number of CD8 + T cells was assessed by counting the number lymphocytes stained brown on the tumor cell membrane by an anti-CD8 antibody.…”

Section: Methodsmentioning

confidence: 99%

The Major Role of NF-κB in the Depth of Invasion on Acral Melanoma by Decreasing CD8+ T Cells

Usman

Hernowo

Tobing

et al. 2018

J Pathol Transl Med

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“…Under physiological and stroke conditions, new functional neurons integrate into the hippocampal network. Studies have shown a correlation between adult neurogenesis and re-learning for solving tasks in similar spatial environments [43][44][45][46]. The need for new neurons in spatial memory has been shown in studies using various ablation models to suppress neurogenesis [14].…”

Section: Discussionmentioning

confidence: 99%

Early Stroke Induces Long-Term Impairment of Adult Neurogenesis Accompanied by Hippocampal-Mediated Cognitive Decline

Kathner-Schaffert

Karapetow

Günther

et al. 2019

Cells

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Stroke increases neurogenesis in the adult dentate gyrus in the short term, however, long-term effects at the cellular and functional level are poorly understood. Here we evaluated the impact of an early stroke lesion on neurogenesis and cognitive function of the aging brain. We hypothesized that a stroke disturbs dentate neurogenesis during aging correlate with impaired flexible learning. To address this issue a stroke was induced in 3-month-old C57Bl/6 mice by a middle cerebral artery occlusion (MCAO). To verify long-term changes of adult neurogenesis the thymidine analogue BrdU (5-Bromo-2′-deoxyuridine) was administrated at different time points during aging. One and half months after BrdU injections learning and memory performance were assessed with a modified version of the Morris water maze (MWM) that includes the re-learning paradigm, as well as hippocampus-dependent and -independent search strategies. After MWM performance mice were transcardially perfused. To further evaluate in detail the stroke-mediated changes on stem- and progenitor cells as well as endogenous proliferation nestin-green-fluorescent protein (GFP) mice were used. Adult nestin-GFP mice received a retroviral vector injection in the hippocampus to evaluate changes in the neuronal morphology. At an age of 20 month the nestin-GFP mice were transcardially perfused after MWM performance and BrdU application 1.5 months later. The early stroke lesion significantly decreased neurogenesis in 7.5- and 9-month-old animals and also endogenous proliferation in the latter group. Furthermore, immature doublecortin (DCX)-positive neurons were reduced in 20-month-old nestin-GFP mice after lesion. All MCAO groups showed an impaired performance in the MWM and mostly relied on hippocampal-independent search strategies. These findings indicate that an early ischemic insult leads to a dramatical decline of neurogenesis during aging that correlates with a premature development of hippocampal-dependent deficits. Our study supports the notion that an early stroke might lead to long-term cognitive deficits as observed in human patients after lesion.

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“…While an association between NM and recurrence has been described [12], to our knowledge we are the first to identify ALM as an independent predictor of recurrence in patients with negative SLNs. 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].…”

mentioning

confidence: 99%

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

Persa

Knuever

Mauch

2019

J Deutsche Derma Gesell

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Tumor infiltrating lymphocytes in acral lentiginous melanoma: a study of a large cohort of cases from Latin America

Abstract: ALM is highly prevalent in Peru and carries poor outcome. Lower TIL levels were associated with poor outcome and ALM.

Cited by 46 publications

References 59 publications

The Major Role of NF-κB in the Depth of Invasion on Acral Melanoma by Decreasing CD8+ T Cells

The Major Role of NF-κB in the Depth of Invasion on Acral Melanoma by Decreasing CD8+ T Cells

Early Stroke Induces Long-Term Impairment of Adult Neurogenesis Accompanied by Hippocampal-Mediated Cognitive Decline

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

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