Art of TIL immunotherapy: SITC's perspective on demystifying a complex treatment.

In a first for solid cancers, cellular immunotherapy has entered standard of care in the treatment of patients with metastatic melanoma. The infusion of autologous tumor-infiltrating T lymphocytes (TIL) is capable of mediating durable tumor regression and is now Food and Drug Administration-approved for patients with disease refractory to immune checkpoint inhibitors. Since the advent of chimeric antigen receptor (CAR) T cells for patients with hematological malignancies, a growing network of centers capable of delivering effector T cell products to patients has developed.

Open-label, phase II study of talimogene laherparepvec plus pembrolizumab for the treatment of advanced melanoma that progressed on prior anti-PD-1 therapy: MASTERKEY-115.

Background: Treatment options for immunotherapy-refractory melanoma are an unmet need. The MASTERKEY-115 phase II, open-label, multicenter trial evaluated talimogene laherparepvec (T-VEC) plus pembrolizumab in advanced melanoma that progressed on prior programmed cell death protein-1 (PD-1) inhibitors.

Methods: Cohorts 1 and 2 comprised patients (unresectable/metastatic melanoma) who had primary or acquired resistance, respectively, and disease progression within 12 weeks of their last anti-PD-1 dose.

LRIG1 engages ligand VISTA and impairs tumor-specific CD8 T cell responses.

Immune checkpoint blockade is a promising approach to activate antitumor immunity and improve the survival of patients with cancer. V-domain immunoglobulin suppressor of T cell activation (VISTA) is an immune checkpoint target; however, the downstream signaling mechanisms are elusive. Here, we identify leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) as a VISTA binding partner, which acts as an inhibitory receptor by engaging VISTA and suppressing T cell receptor signaling pathways.

Autologous human preclinical modeling of melanoma interpatient clinical responses to immunotherapeutics.

Background: Despite recent advances in immunotherapy, a substantial population of late-stage melanoma patients still fail to achieve sustained clinical benefit. Lack of translational preclinical models continues to be a major challenge in the field of immunotherapy; thus, more optimized translational models could strongly influence clinical trial development. To address this unmet need, we designed a preclinical model reflecting the heterogeneity in melanoma patients' clinical responses that can be used to evaluate novel immunotherapies and synergistic combinatorial treatment strategies.

Plain language summary of the CheckMate 76K study results: nivolumab given after stage 2B/2C melanoma is removed by surgery.

What Is This Summary About?: In this article, we summarize results from the ongoing phase 3 CheckMate 76K clinical study published online in in October 2023. The study goal was to learn whether nivolumab works as an adjuvant therapy (that is, helps to keep cancer from coming back when it is given after surgery) for stage 2 melanoma (skin cancer) that has not spread to other parts of the body. Nivolumab is an immunotherapy that activates a person's immune system so it can destroy cancer cells.

BETA prime: a first-in-man phase 1 study of AdAPT-001, an armed oncolytic adenovirus for solid tumors.

AdAPT-001 is an oncolytic adenovirus (OAV) with a transforming growth factor beta (TGF-ß) trap, which neutralizes the immunosuppressive and profibrotic cytokine, TGF-ß. The aim or purpose of this phase 1 study was to assess the safety and tolerability and, secondarily, the efficacy of AdAPT-001 after single intratumoral injection (IT) (Part 1) and multidose IT injection (Part 2) in patients with superficially accessible, advanced refractory solid tumors. Part 1 enrolled 9 patients with a 3 + 3 single dose-escalation safety run-in involving 2.

Clinical and Immunologic Features of Germline Pathogenic Variant-Positive Patients with Melanoma.

Purpose: Malignant melanoma represents the most lethal skin cancer with germline predispositions thought to comprise 10% to 15% of all melanoma cases. No studies to date examine the immunologic features that may differentiate survival differences between germline pathogenic variant (gPV)-positive patients with melanoma from gPV-negative patients with melanoma.

Experimental Design: Adult patients with melanoma and clinical characteristics suggesting hereditary predisposition to cancer were prospectively recruited to undergo germline testing and flow cytometric analysis of peripheral immune suppressor cells.

A transcriptional evaluation of the melanoma and squamous cell carcinoma TIL compartment reveals an unexpected spectrum of exhausted and functional T cells.

Introduction: Significant heterogeneity exists within the tumor-infiltrating CD8 T cell population, and exhausted T cells harbor a subpopulation that may be replicating and may retain signatures of activation, with potential functional consequences in tumor progression. Dysfunctional immunity in the tumor microenvironment is associated with poor cancer outcomes, making exploration of these exhausted T cell subpopulations critical to the improvement of therapeutic approaches.

Methods: To investigate mechanisms associated with terminally exhausted T cells, we sorted and performed transcriptional profiling of CD8 tumor-infiltrating lymphocytes (TILs) co-expressing the exhaustion markers PD-1 and TIM-3 from large-volume melanoma tumors.

Adjuvant nivolumab in resected stage IIB/C melanoma: primary results from the randomized, phase 3 CheckMate 76K trial.

Patients with resected stage IIB/C melanoma have high recurrence risk, similar to those with resected stage IIIA/B disease. The phase 3, double-blind CheckMate 76K trial assessed 790 patients with resected stage IIB/C melanoma randomized 2:1 (stratified by tumor category) to nivolumab 480 mg or placebo every 4 weeks for 12 months. The primary endpoint was investigator-assessed recurrence-free survival (RFS).

Neuroendocrine lineage commitment of small cell lung cancers can be leveraged into p53-independent non-cytotoxic therapy.

Small cell lung cancers (SCLCs) rapidly resist cytotoxic chemotherapy and immune checkpoint inhibitor (ICI) treatments. New, non-cross-resistant therapies are thus needed. SCLC cells are committed into neuroendocrine lineage then maturation arrested.

Perspectives in Melanoma: meeting report from the Melanoma Bridge (December 1st-3rd, 2022-Naples, Italy).

Outcomes for patients with melanoma have improved over the past decade with the clinical development and approval of immunotherapies targeting immune checkpoint receptors such as programmed death-1 (PD-1), programmed death ligand 1 (PD-L1) or cytotoxic T lymphocyte antigen-4 (CTLA-4). Combinations of these checkpoint therapies with other agents are now being explored to improve outcomes and enhance benefit-risk profiles of treatment. Alternative inhibitory receptors have been identified that may be targeted for anti-tumor immune therapy, such as lymphocyte-activation gene-3 (LAG-3), as have several potential target oncogenes for molecularly targeted therapy, such as tyrosine kinase inhibitors.

Routine imaging guided by a 31-gene expression profile assay results in earlier detection of melanoma with decreased metastatic tumor burden compared to patients without surveillance imaging studies.

Patients with early-stage disease typically have a good prognosis, but still have a risk of recurrence, even with negative sentinel lymph node biopsy (SLNB). This study explores the utility of routine imaging to detect metastases in patients with negative SLNB but high-risk 31 gene expression profile (31-GEP) scores. We retrospectively identified melanoma patients with negative SLNBs.

Prophylactic Lymphaticovenous Anastomosis Performed with Lymphadenectomy is Oncologically Safe for Melanoma.

Background: A major concern of lymphaticovenous anastomosis (LVA), which has not been studied, is increased risk of metastasis. Melanoma patients with macrometastatic lymph node disease represent a high-risk group for recurrence and metastasis. On the basis of a literature review, this present study is the first to evaluate the impact of prophylactic LVA on cancer survival and recurrence.

Maxillary and Mandibular Healing After Facial Allotransplantation.

Introduction: Facial transplantation has emerged as a viable option in treating devastating facial injuries.Despite the high healing rate of Le Fort III and bilateral sagittal split osteotomies (BSSO) in nontransplant patients, few studies have reported assessment of maxillary and mandibular healing in face transplant patients compared with nontransplant patients. The aim of this study was to examine differences in bone healing in our patients.

Best practices in surgical and nonsurgical management of head and neck Merkel cell carcinoma: An update.

Merkel cell carcinoma (MCC) is a rare, highly aggressive cutaneous neuroendocrine carcinoma. Controversy exists regarding optimal management of MCC as high-quality randomized studies and clinical trials are limited, and physicians are bound to interpret highly heterogeneous, retrospective literature in their clinical practice. Furthermore, the rising incidence and notably poor prognosis of MCC urges the establishment of best practices for optimal management of the primary tumor and its metastases.