Can we yet use tertiary lymphoid structures as predictive biomarkers for immunotherapy response in melanoma?

PURPOSE OF REVIEW: In this review, we explore the potential of tertiary lymphoid structures (TLS) as predictive biomarkers in the response to immunotherapy for melanoma patients. RECENT FINDINGS: The significance of TLS as indicators predicting immunotherapy response becomes particularly pronounced. Melanoma, renowned for its aggressive characteristics, has undergone revolutionary transformations in treatment through immunotherapeutic interventions. Investigations have unveiled a compelling correlation between the presence of TLS in the melanoma tumor microenvironment and favorable responses to immunotherapy. These responses, characterized by heightened survival rates and improved clinical outcomes, imply that TLS might be pivotal in tailoring more efficient and personalized treatments for individuals with melanoma. The ongoing discourse regarding TLS as a predictive biomarker underscores the need for a meticulous examination of its potential in guiding clinical decisions and optimizing therapeutic strategies. SUMMARY: TLS show great promises as potential biomarkers to melanoma patient's outcomes in ICI treatment; however, more studies are needed to understand their mechanisms of actions and the long-term impact of their functionality.

Single agent vs combination immunotherapy in advanced melanoma: a review of the evidence.

PURPOSE OF REVIEW: The aim of this review is to outline the current landscape of advanced melanoma treatment options, provide insights on selecting combination therapies within different clinical scenarios, capture clinical relevance of anti-programmed cell death protein 1 (PD-1) monotherapy, and explore the unmet needs with immune check-point inhibitors (ICI) in advanced melanoma. RECENT FINDINGS: ICI based treatment consisted of single agent ICI or dual combination ICI-ICI is the standard of care of front-line treatment of metastatic or unresectable melanoma. PD-1 inhibitors (Pembrolizumab and Nivolumab) improved progression free survival (PFS) and overall survival (OS) compared to chemotherapy and cytotoxic T-lymphocyte associated protein 4 (CTLA-4) inhibitors (Ipilimumab and Tremelimumab). The dual ICI combination (Nivolumab and Ipilimumab) provided profound and durable responses better than monotherapy, and the longest overall survival ever achieved in advanced disease, including in patients with murine sarcoma viral oncogene homolog B (BRAF)-mutated disease, but at the cost of a high risk of severe toxicity. The new dual blockage of LAG-3 and PD-1 (Nivolumab-Relatlimab) emerges as a valid option with promising efficacy outcomes and a favourable toxicity profile. Mature survival data is still needed to capture the real benefit. SUMMARY: These new plethora of options pose new challenges not only for optimal treatment sequencing strategies but especially for management of adverse effects, endorsing the need to integrate a holistic and personalized approach for patient care.