Although a subset of clear cell renal cell carcinoma (ccRCC) patients respond to immune checkpoint blockade (ICB), predictors of response remain uncertain. We investigated whether abnormal expression of endogenous retroviruses (ERVs) in tumors is associated with local immune checkpoint activation (ICA) and response to ICB. Twenty potentially immunogenic ERVs (πERVs) were identified in ccRCC in The Cancer Genome Atlas data set, and tumors were stratified into 3 groups based on their expression levels. πERV-high ccRCC tumors showed increased immune infiltration, checkpoint pathway upregulation, and higher CD8+ T cell fraction in infiltrating leukocytes compared with πERV-low ccRCC tumors. Similar results were observed in ER+/HER2- breast, colon, and head and neck squamous cell cancers. ERV expression correlated with expression of genes associated with histone methylation and chromatin regulation, and πERV-high ccRCC was enriched in BAP1 mutant tumors. ERV3-2 expression correlated with ICA in 11 solid cancers, including the 4 named above. In a small retrospective cohort of 24 metastatic ccRCC patients treated with single-agent PD-1/PD-L1 blockade, ERV3-2 expression in tumors was significantly higher in responders compared with nonresponders. Thus, abnormal expression of πERVs is associated with ICA in several solid cancers, including ccRCC, and ERV3-2 expression is associated with response to ICB in ccRCC.
Tumor lysis syndrome (TLS) refers to a constellation of metabolic abnormalities that result from release of intracellular solutes (potassium, phosphate, and nucleic acid metabolites) from rapidly dying tumor cells. While TLS most commonly occurs following chemotherapy, spontaneous TLS can rarely occur in rapidly dividing liquid or solid malignancies. Here, we report the cases of two patients who presented with non-specific symptoms and were found to have spontaneous TLS. Work-up in both cases led to a diagnosis of T-cell malignancy (i.e., acute lymphoblastic leukemia and angioimmunoblastic lymphoma). Given that spontaneous TLS can be the first manifestation of an underlying malignancy, all physicians should be familiar with this oncologic emergency. Early recognition and prompt management can be lifesaving for patients with an otherwise curable malignancy.
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