Exceptional response to nivolumab of a heavily pre-treated patient with metastatic renal-cell cancer: from a case report to molecular investigation and future perspectives

Immunotherapy may result in long-lasting exceptional clinical responses, the molecular background of which is inadequately understood. Here, we present the case of a 63-year-old patient with a past medical history of renal cancer who relapsed many years later. Several treatment lines were administered prior to immunotherapy, which was administered in the ninth line, achieving complete remission which had lasted for more than 3 years. Genomic alterations, tumor mutational burden (TMB), and microsatellite instability as well as PD-L1, MLH1, MSH2, MSH6, PMS2, CD3, CD8, CD20, CD138, CD1a, and FoxP3 expression were assessed in primary and metastatic tumors. Primary and metastatic tumors were microsatellite stable with high TMB, while somatic mutations in MLH1 and TP53 genes were detected, respectively. Although the primary tumor was negative for PD-L1 expression, the lung metastasis was positive. Interestingly, metastasis displayed a dramatically increased infiltration by CD1a-positive dendritic cells in addition to increased CD3+ and CD8+ cytotoxic T cells. Increased infiltration of the metastatic tumor by CD1a+ antigen presenting cells warrants further investigation to assess its potential predictive value.