ABSTRACT
Immune checkpoint inhibition has shown success in treating metastatic cutaneous melanoma but has limited efficacy against metastatic uveal melanoma, a rare variant arising from the immune privileged eye. To better understand this resistance, we comprehensively profile 100 human uveal melanoma metastases using clinicogenomics, transcriptomics, and tumor infiltrating lymphocyte potency assessment. We find that over half of these metastases harbor tumor infiltrating lymphocytes with potent autologous tumor specificity, despite low mutational burden and resistance to prior immunotherapies. However, we observe strikingly low intratumoral T cell receptor clonality within the tumor microenvironment even after prior immunotherapies. To harness these quiescent tumor infiltrating lymphocytes, we develop a transcriptomic biomarker to enable in vivo identification and ex vivo liberation to counter their growth suppression. Finally, we demonstrate that adoptive transfer of these transcriptomically selected tumor infiltrating lymphocytes can promote tumor immunity in patients with metastatic uveal melanoma when other immunotherapies are incapable.
Subject(s)
Melanoma , Skin Neoplasms , Uveal Neoplasms , Humans , Melanoma/genetics , Melanoma/therapy , Uveal Neoplasms/genetics , Uveal Neoplasms/therapy , Lymphocytes, Tumor-Infiltrating , Immunotherapy , Tumor Microenvironment/geneticsABSTRACT
BACKGROUND: Renal artery aneurysm (RAA) is a rare condition that involves dilation of all layers of the arterial wall of the renal artery. The risk of rupture is rare, but intervention is recommended for larger aneurysms. Surgical decision-making regarding live donor renal transplantation (LDRT) centers around safety for the living donor, and laterality of the donated kidney is based on providing the donor with the best longevity pertaining to the remaining kidney. We looked to review our long-term outcomes surrounding live donor transplants from donors with RAA with ex vivo resection and reconstruction prior to implantation. METHODS: A retrospective review was done of all laparoscopic live donor transplant nephrectomies with ex vivo aneurysm resection, reconstruction, and implantation at a single center. RESULTS: Three pairs of patients underwent successful laparoscopic donor nephrectomy, RAA resection, reconstruction, and transplantation of kidney. 2 males and 1 female ages 47 to 58 years of age underwent transplantation. The donors at 5 years of follow-up were noted to be functioning appropriately with no long-term sequelae of their donation and a mean remanent kidney function of 63 mL/min. DISCUSSION: For potential live donors with asymptomatic, unilateral renal artery aneurysm and no systemic disease, live donation with ex vivo resection and reconstruction can be performed with excellent long-term donor and recipient outcomes.
Subject(s)
Aneurysm , Renal Artery , Male , Humans , Female , Renal Artery/surgery , Kidney , Aneurysm/surgery , Living Donors , PatientsABSTRACT
Heterotopic ossification (HO) is the abnormal formation of extra-skeletal bone in soft tissue, which can occur after trauma or surgery. HO in joints can cause pain, hinder mobility, and compress surrounding nerves and blood vessels. We present an unusual case of arterial insufficiency caused by HO in the right popliteal fossa.
