Thoracic and cutaneous sarcoid-like reaction associated with anti-PD-1 therapy: longitudinal monitoring of PD-1 and PD-L1 expression after stopping treatment

Abstract

BackgroundImmune checkpoint inhibitors (ICI) target T cell inhibitory pathways that are responsible for cancer tolerance by down-modulating immune functions. ICI have revolutionized patients care with lung cancer. Nevertheless, restoring endogenous antitumor T-cell responses can induce immune related adverse events, such as sarcoidosis.Case presentationWe report here the first case of a thoracic and cutaneous sarcoid-like reaction in a patient with a relapsing unresectable non-small cell lung cancer (NSCLC) treated with nivolumab, an anti-PD-1 mAb. The expression of PD-1 and its ligands, PD-L1 and PD-L2, was assessed by flow cytometry on peripheral blood mononuclear cells (PBMC) and compared to patients who had discontinued nivolumab therapy without having developed any immune related adverse events. PD-L1 expression was transiently increased on B cells, T cells and monocytes, whereas PD-L2 expression was not modulated. PD-1 was transiently undetectable when PD-L1 was maximal, before returning to basal level. Sarcoidosis spontaneously resolved, without corticotherapy.ConclusionThis case sheds the light on a complex regulation of PD-L1 expression in vivo on PBMC after nivolumab arrest and triggers the question of monitoring the expression of immune checkpoint on immune cells during and after treatment with ICI.

Immune-Related Erythema Nodosum Mimicking in Transit Melanoma Metastasis on [18F]-FDG PET/CT

“…PET/CT exam also revealed the appearance of several FDG-avid subcutaneous nodules on her legs ( e ) no pathologic uptake and ( j ) SUVmax 10.5 on the left leg and 10.2 on the right leg. Such findings have been reported in patients with non-small cell lung cancer [ 1 ], esophageal cancer [ 2 ], and ocular melanoma [ 3 ] treated by PD-1 inhibitors. Similar images have also been published in metastatic cutaneous melanoma treated by BRAF and MEK inhibitors [ 4 ].…”

Nodal immune flare mimics nodal disease progression following neoadjuvant immune checkpoint inhibitors in non-small cell lung cancer

“…The biological mechanisms underlying NIF are unclear and it remains to be determined whether NIF correlates with enhanced antitumor immunity. In previous reports, the pathological assessment of enlarged and avid nodes revealed sarcoid-like changes and elevated expression of PD-L1 on peripheral immune cells upon discontinuation of ICI therapy in NSCLC 15 . The investigators found that an elevated expression of PD-L1 by peripheral blood mononuclear cells was associated with nodal and skin sarcoid-like reaction after nivolumab was discontinued in a case of unresectable NSCLC 15 .…”

“…In previous reports, the pathological assessment of enlarged and avid nodes revealed sarcoid-like changes and elevated expression of PD-L1 on peripheral immune cells upon discontinuation of ICI therapy in NSCLC 15 . The investigators found that an elevated expression of PD-L1 by peripheral blood mononuclear cells was associated with nodal and skin sarcoid-like reaction after nivolumab was discontinued in a case of unresectable NSCLC 15 . The authors speculated that the increase in peripheral PD-L1 may result from cytokines produced by activated immune cells present in sarcoid lesions and/or in the periphery 15 , 16 .…”

Chronic activation of 4-1BB signaling induces granuloma development in tumor-draining lymph nodes that is detrimental to subsequent CD8+ T cell responses

“…Although we suggest that all ICB-boosting T cell responses in TDLNs, including production of agonistic anti-4-1BB and antagonistic anti-PD-1 mAbs, may have the potential to lead to the development of granulomas in TDLNs due to the excessive accumulation of IFN-γ-producing T cells, recent clinical reports indicate that sarcoidosis in LN adjacent tumor tissues developed in some cancer patients with good oncologic responses to PD-1 blockade, 10,39 and the repeated injection of anti-4-1BB mAb was generally beneficial to suppressing tumor growth ( Fig. 1b), even though the granuloma was developed in inguinal TDLNs (Fig.…”