T/NK-cell neoplasms represent rare and highly diverse cancers, distinguished by variability in their molecular architecture, local inflammatory milieu, and microenvironmental composition, which collectively underpin the diversity of clinical presentations and outcomes. The neoplastic tissue comprises malignant lymphoma/leukemic cells in concert with a spectrum of stromal elements and the acellular extracellular matrix (ECM), collectively constituting the lymphoma microenvironment (LME). These components engage in dynamic, reciprocal interactions, forming a self-regulating ecosystem capable of responding adaptively to both exogenous and endogenous stimuli. Historically, the LME was largely neglected in considerations of lymphomagenesis; however, emerging evidence highlights its pivotal role in driving core oncogenic processes, including sustained proliferative signaling, angiogenesis, immune evasion, and apoptotic resistance. Deciphering the intricate, multidirectional crosstalk among the cellular and acellular constituents of the T/NK-cell neoplastic microenvironment promises to deepen our understanding of disease biology and may inform the development of novel, mechanism-based therapeutic interventions.

Background/Objectives: This study evaluates the prognostic value of baseline inflammatory biomarkers, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), and pan-immune-inflammation value (PIV) in advanced cutaneous melanoma treated with first-line immunotherapy. Methods: This multicenter retrospective study included 162 patients with unresectable stage III/IV cutaneous melanoma treated with first-line pembrolizumab, nivolumab, or nivolumab plus ipilimumab. Biomarkers were calculated from complete blood counts obtained within 30 days before treatment start. Cut-offs were defined by ROC analysis. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan–Meier and Cox regression. Response was assessed by RECIST v1.1. Results: Higher baseline NLR, PLR, MLR, SII, and PIV were more common in patients with adverse baseline features, including liver metastases, elevated LDH, and poorer ECOG performance status. Patients with biomarker values below the cut-offs had significantly longer PFS and OS. In biomarker-specific multivariable models adjusted for selected clinical covariates, PIV retained the most consistent association with PFS and OS, while MLR was associated with PFS, and PLR with OS. Conclusions: Baseline inflammatory biomarkers from routine blood counts provide useful prognostic information in advanced melanoma treated with first-line ICIs. PIV showed the most consistent association with survival outcomes and may support initial risk stratification alongside LDH, ECOG, and metastasis pattern. However, prospective validation in independent cohorts is needed before routine clinical implementation.

Background/Objectives: This study evaluates the prognostic value of baseline inflam-matory biomarkers neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII) and pan-immune-inflammation value (PIV) in advanced cutaneous melanoma treated with first-line immunotherapy. Methods: This multicenter retrospective study included 162 patients with unresectable stage III/IV cutaneous melanoma treated with first-line pembrolizumab, nivolumab, or nivolumab plus ipilimumab. Biomarkers were calculated from complete blood counts obtained within 30 days before treatment start. Cut-offs were defined by ROC analysis. Progression free survival (PFS) and overall survival (OS) were analyzed using Kaplan–Meier and Cox regression. Response was assessed by RECIST v1.1. Results: Higher baseline NLR, PLR, MLR, SII and PIV were more common in patients with adverse baseline features, including liver metastases, elevated LDH and poorer ECOG performance status. Patients with biomarker values below the cut-offs had sig-nificantly longer PFS and OS. In multivariable models adjusted for clinical covariates, PIV remained independently associated with the duration of PFS and OS; MLR inde-pendently predicted PFS, while PLR independently predicted OS. Conclusions: Baseline inflammatory biomarkers from routine blood counts provide useful prognostic information in advanced melanoma treated with first-line ICIs. PIV showed the most consistent independent association with survival outcomes and may support initial risk stratification alongside LDH, ECOG and metastasis pattern. However, prospective validation in independent cohorts is needed before routine clinical implementation.

Immune checkpoint inhibitors (ICIs) immensely improved outcomes in melanoma patients. Vitiligo-like depigmentation (VLD) is a well-documented adverse event of ICIs which is well tolerated and often associated with prolonged response to treatment. The aim of this study was to assess the effect of VLD occurrence on survival in melanoma patients treated with ICIs. We conducted a retrospective analysis among unresectable stage III and stage IV melanoma patients treated with pembrolizumab or nivolumab at the University Clinical Center Niš from May 2017 to February 2024. The Chi-square or Fisher’s exact test were used to evaluate the categorical variables. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method (CI 95%; p < 0.05). Survival between the patients with or without VLD was compared using a log-rank (p < 0.05). A total of 109 patients were included, including 22 patients who developed VLD (20.2%). Median follow-up in the VLD group was 39.4 months, with 59% still alive and progression-free three years after treatment initiation. The overall response rate (ORR) was 72.7% vs. 29.9%, with 31.8% vs. 13.8% of complete responses in favor of the VLD subgroup. The occurrence of VLD was associated with significantly longer median PFS (8.148 vs. 52.862 months; p = 0.0001) and median OS (12.715 vs. NR months; p = 0.0001). Prediction of VLD occurrence is not possible, therefore, it cannot be a predictive parameter per se, however, it can be associated with prolonged response to ICI treatment in patients who develop this adverse event.

Background: To evaluate the efficacy of combined targeted therapy and immunotherapy in patients with BRAF-mutated melanoma, and to assess the prognostic significance of lactate dehydrogenase (LDH) activity. Methods: This retrospective study included 68 patients (mean age 57.4±13.6 years), with advanced melanoma treated at a tertiary centre between 2019 and 2024. Patients were divided into two groups: immunotherapy (nivolumab/pembrolizumab) and combined BRAF/ MEK-targeted therapy (dabrafenib/trametinib or vemurafenib/cobimetinib). Clinical outcomes were analysed according to LDH values. Results: Median progression-free survival (PFS) was 15.97 months, while median overall survival (OS) reached 38.57 months in our patient population. No statistically significant differences were observed between treatment groups, although numerically longer survival was noted in the immunotherapy group. Elevated LDH activity was detected in 41% of patients, more frequently among those receiving targeted therapy. Patients with normal LDH activity had significantly longer OS than those with elevated LDH (NR vs 16.6 months; p=0.009). Conclusion: Established prognostic value of LDH was firmed in our patient population. Patients with LDH activity within the reference range had significantly longer overall survival, underscoring LDH's importance as a routine biomarker in clinical practice. Immunotherapy showed numerically better outcomes than combined BRAF/MEK therapy, highlighting the need for further prospective studies to validate these findings.