We report the initial case of EBV-positive classic Hodgkin lymphoma (cHL) after guselkumab therapy for psoriasis. High-plex spatial proteomic analysis showed a Th2-polarized immunosuppressive tumor microenvironment, indicating immune reprogramming from IL-23 inhibition might have triggered the onset of EBV-positive cHL.

The authors have declared no competing interest.

Funds supporting this study were from NCI/NIH R01 CA269660-01 (EC and JFB), U54 CA272686 (EC) and the comprehensive cancer center core grant P30 CA006927 in support of the histopathology (housing the spatial high-plex proteomic seqIF and digital analysis branch) facilities at the Fox Chase Cancer center. In addition, funds supporting this study were obtained from the ACS grant RP-23-1070169-01-WRP (EC), The trustees of the Community Foundation of New Jersey on behalf of Mrs. Marina P Zazanis (EC), The Pancreatic Cure Foundation (EC, JFB, MD), and the 5th AHEPA Cancer Research Foundation, Inc. (EC). The preliminary findings from this study were presented by B.S. before the expert panel as part of the oral presentation, titled Classic Hodgkin lymphoma, EBV+, following immunomodulator therapy (IL-23 inhibitor) for Psoriasis at the 22nd Meeting of the European Association for Hematopathology, held in Dubrovnik, Croatia, Sep 21-Sep 26, 2024. The authors thank Dr. J. Kowal and E. Geneletti, current or former Lunaphore employees, for their expertise and support in developing the high-plex immunofluorescence analysis using HORIZON image analysis software from the COMET suite.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The biospecimens and clinical data being utilized in this tumor microenvironment study were collected previously as part of the patient's routine clinical care. No separate specimens were collected for the study. The Institutional Review Board of Fox Chase Cancer Center provided ethical approval for this work. All authors state that the presented material does not include any information, unique characteristics or identifiers that could be used alone or in combination with other information to identify, directly or indirectly, an individual who is a subject of the case report.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

All data produced in the present study are available upon reasonable request to the authors

Detailed materials and methods, including spatial single-cell high-plex seqIF™ staining protocol, methodology for data preprocessing, filtering and analysis (cell segmentation, supervised and unsupervised phenotyping and spatial analysis) and the original OME-TIFF files containing the multiplex immunofluorescence data underlying the findings described in this manuscript will be made available upon reasonable request to the corresponding author.