Humoral and cellular correlates of a novel immune-related adverse event and its treatment

Abstract

Immune-related adverse events (irAE) may affect almost any organ system and occur at any point during treatment with immune checkpoint inhibitors (ICI). We present a patient with advanced lung cancer receiving antiprogrammed death 1 checkpoint inhibitor who developed a delayed-onset visual irAE treated with corticosteroids. Through assessment of longitudinal biospecimens, we analyzed serial autoantibodies, cytokines, and cellular populations. Months after ICI initiation and preceding clinical toxicity, the patient developed broad increases in cytokines (most notably interleukin-6 (IL-6), interferon-γ (IFNγ), C-X-C motif chemokine ligand 2 (CXCL2), and C–C motif chemokine ligand 17 (CCL17)), autoantibodies (including anti-angiotensin receptor, α-actin, and amyloid), CD8 T cells, and plasmablasts. Such changes were not observed in healthy controls and ICI-treated patients without irAE. Administration of corticosteroids resulted in immediate and profound decreases in cytokines, autoantibodies, and inflammatory cells. This case highlights the potential for late-onset changes in humoral and cellular immunity in patients receiving ICI. It also demonstrates the biologic effects of corticosteroids on these parameters. Application of humoral and cellular immune biomarkers across ICI populations may inform toxicity monitoring and management.

Checkpoint inhibitor immune-related adverse events: A focused review on autoantibodies and B cells as biomarkers, advancements and future possibilities

“…A longitudinal assessment of blood in an advanced lung cancer patient who developed late-onset irAEs on PD-1 inhibition, also reported increases in plasmablasts in circulation ( 119 ). Using functional ex vivo assays and mass cytometry analysis, defects in the regulatory B cell repertoire was found to predispose NSCLC patients to the development of immune related toxicity following anti-PD-1(L1) blockade ( 120 ).…”

Comparative Analysis of Dimension Reduction Methods for Cytometry by Time-of-Flight Data

“…Table 2 ). These include the TuPro cohort(9), the Oetjen cohort(22), the CyAnno cohort(33), the LG cohort(34), the Brain cohort(35), the BC cohort(36), the Levine32 cohort(37), the Levine13 cohort(37), the Samusik cohort(38), the Lung cancer cohort(39), and the Covid cohort. For all datasets, we either obtained their cell typing results from the original publications, or performed cell typing ourselves based on clustering of the cells according to their proteomics features followed by manual assignment according to expression of marker genes.…”

“…The public CyTOF and scRNA-seq data used in this study were from citations 9,11,23,[43][44][45][46][47][48][50][51][52] and described in Sup. We define complementarity as the likelihood of obtaining a top-performing method for a given dataset by choosing a specific DR method.…”

“…The public CyTOF and scRNA-seq data used in this study were from citations 9,11,25,[44][45][46][47][48][49][51][52][53] and described in Sup. The DR methods reviewed in this study, their basic characteristics described in text, and their performances in terms of accuracy, scalability, stability, and utility.…”

Uveitisinduktion durch immunonkologische Therapien, speziell Checkpoint-Inhibitoren

“…Diese korrelieren mit dem Auftreten bestimmter immunbedingter Nebenwirkungen der ICI und normalisieren sich mit dem Ansprechen der systemischen Steroidtherapie rasch [43]. Ein unmittelbarer und ausgeprägter Steroideffekt lässt sich auch auf die humorale und zelluläre Immunreaktion nachweisen [44], was eine nach klinischer Maßgabe möglichst frühe Dosisreduktion der Steroide zugunsten der ICI-Wirkung auf die Tumorprogression nahelegt. Die Früherkennung immunvermittelter Nebenwirkungen der ICI-Therapie und eine sofortige Behandlung tragen darüber hinaus zu einem besseren Ansprechen auf niedrige Steroiddosen bei und reduzieren damit auch das Risiko, die ICI-Therapie wegen dieser Nebenwirkungen absetzen zu müssen.…”