Tubulointerstitial nephritis as adverse effect of programmed cell death 1 inhibitor, nivolumab, showed distinct histological findings

Abstract

Immune-checkpoint inhibitor nivolumab (anti-PD-1 antibody) blocks T cell inhibition and stimulate immunologic response toward cancer cells. It was also revealed that PD-1/PD-L1 interaction crucially controls the effector differentiation of auto-reactive T cells to maintain self-tolerance. Therefore, potential autoimmunological side-effect can occur in any organ. Here, we report a case of 67-year-old Japanese male with lung adenocarcinoma treated with nivolumab who developed acute tubulointerstitial nephritis after the third infusion of nivolumab. Kidney biopsy showed distinct histological findings: Proliferation of CD38 positive and IgG positive plasma cells, and affluent infiltration of FoxP3? regulatory T cells. Herein, we do pathological discussion concerning acute tubulointerstitial nephritis occurred in this case based on these histological findings.

Successful treatment with nivolumab for lung cancer with low expression of PD‐L1 and prominent tumor‐infiltrating B cells and immunoglobulin G

“…In a mouse model, PD‐1 blockade enhanced the response to the antigen‐specific antibody by promoting the accumulation of helper T cells . In a case of nivolumab‐induced interstitial nephritis, IgG + plasma cells and T cells accumulated in the kidney . Nivolumab can facilitate humoral immunity against cancers, as well as cell‐mediated immunity.…”

“…14 In a case of nivolumab-induced interstitial nephritis, IgG + plasma cells and T cells accumulated in the kidney. 15 Nivolumab can facilitate humoral immunity against cancers, as well as cell-mediated immunity. Investigations of humoral immunity using tissue biopsy specimens before and after nivolumab therapy may shed light on this issue.…”

The Analysis of Renal Infiltrating Cells in Acute Tubulointerstitial Nephritis Induced by Anti-PD-1 Antibodies: A Case Report and Review of the Literature

“…AKI with a histological feature of acute tubulointerstitial nephritis is a severe condition and represents the most common ICI-associated renal irAE ( 5 - 8 , 10 - 13 ). Shirali et al reported six cases of AKI and acute tubulointerstitial nephritis, which occurred during treatment with one of the anti-PD-1 antibodies (nivolumab or pembrolizumab) ( 7 ).…”

“…Table summarizes the previously reported cases in which infiltrating cells in the interstitium were analyzed by immunohistochemistry ( 8 , 10 - 13 ). CD3 + T cells were the major infiltrating cells in the kidney.…”

“…The spectrum of irAEs ranges from common manifestations such as dermatological, gastrointestinal and endocrine events, to rare organ damage involving the nervous, hematopoietic, and urinary systems ( 3 ). Specifically, in the urinary system, acute kidney injury (AKI) is clinically important; an increased number of reports on ICI-induced renal injuries has been observed in recent years ( 5 - 13 ).…”