TY - JOUR T1 - Clinical and immunologic correlates of response to PD-1 blockade in a patient with metastatic renal medullary carcinoma JF - Journal for ImmunoTherapy of Cancer JO - J Immunother Cancer DO - 10.1186/s40425-016-0206-1 VL - 5 IS - 1 SP - 1 AU - Kathryn E. Beckermann AU - Pradeep C. Jolly AU - Ju Y. Kim AU - Jennifer Bordeaux AU - Igor Puzanov AU - W. Kimryn Rathmell AU - Douglas B. Johnson Y1 - 2017/12/01 UR - http://jitc.bmj.com/content/5/1/1.abstract N2 - Background Renal medullary carcinoma (RMC) is a rare kidney tumor that occurs in adolescent and young adults, typically in association with sickle cell trait. RMC exhibits rapid disease progression, frequent metastases at diagnosis, and dismal clinical outcomes. Currently available therapies, including cisplatin-based combination chemotherapy, multi-tyrosine kinase, and mTOR inhibitor strategies demonstrate either transient responses or minimal activity. Therefore, further molecular characterization and additional treatment strategies are urgently needed in this aggressive disease. The role of immune system surveillance and responsiveness to anti-PD-1 therapies in RMC are completely unexplored.Case presentation A 29 year old male with sickle cell trait presented with painless hematuria that ultimately resulted in a diagnosis of RMC. He underwent total nephrectomy and adjuvant cytotoxic chemotherapy with carboplatin, gemcitabine, paclitaxel, and bevacizumab. As is common in this aggressive form of kidney cancer he recurred with biopsy proven lymph node metastasis. He was started on checkpoint inhibitor therapy with nivolumab that inhibits program cell death protein 1 (PD-1), and on his first follow-up imaging he was found to have a partial response that on subsequent scans ultimately resulted in a complete response lasting greater than nine months. In this report, we present a patient with metastatic RMC who exhibited a clinical response to nivolumab, as well as the genetic and immunologic correlates of the pre-treatment tumor. Provocatively, robust immune infiltrate and expression of immune checkpoints were observed, despite the presence of a low mutation burden.Conclusions Here, we report the first case of immune microenvironment profiling and response to anti-PD-1 in a patient with RMC to our knowledge. This case suggests that anti-PD-1 based therapies may have clinical activity in RMC.Abbreviations:(AJCC)American joint comission on cancer(AUC)Area under the curve(CT)Computed tomography(CTLA-4)Cytotoxic T-lymphocyte associated protein 4(FDA)Food and drug administration(mTOR)Mammalian target of rapamycin(PD-1)Progammed cell death 1 protein(PD-L1)Programmed death ligand-1(PET)Positron emission tomography(RCC)Renal cell carcinoma(RMC)Renal medullary carcinoma(SMARCB1)SWI/SNF Related matrix associated actin dependent regulator of chromatin ER -