Miho Takahashi*, Hitoshi Tsuchihashi and Rei Watanabe

J. Cutan. Immunol. Allergy, 13 March 2025 Volume 8 – 2025 | https://doi.org/10.3389/jcia.2025.14441

A 41-year-old woman had been diagnosed with generalized pustular psoriasis (GPP) for 4 years. Her symptoms had been stabilized with cyclosporine (2 mg/kg/day). Despite increasing the cyclosporine dosage to 3 mg/kg/day, the skin lesions did not improve and the patient developed a fever.  A CT scan revealed a mass lesion measuring 2.5 cm × 4 cm in the right breast and axillary lymphadenopathy. Based on the CT findings, the patient was suspected of having left breast cancer. To manage GPP, granulocyte and monocyte adsorption (GMA) was initiated to minimize the possible adverse effects on the suspected cancer. During the five courses of GMA, the patient’s body temperature returned to a normal degree and the pustules and erythema gradually improved. However, the erythema on her trunk remained. GMA was selected as the initial treatment because the therapeutic strategy for the breast cancer had not yet been determined. Meanwhile, etretinate, corticosteroids, biologics, and their combination are also strong candidates for acute exacerbated GPP. Subsequently, subcutaneous brodalumab administration was introduced; brodalumab allowed the patient to concurrently undergo chemotherapy for breast cancer. The patient underwent a left breast mastectomy and was diagnosed with right breast cancer with right axillary lymph node metastasis. The patient started hormonal therapy, and tumor markers showed a decreasing trend. However, she gradually developed skin metastases, which grew despite treatment. The patient died of breast cancer 4 years after diagnosis. Brodalumab was continued for 4 years, during which no recurrence of GPP was observed.

In conclusion, due to the rarity of the disease, selecting an appropriate therapy for GPP is often challenging especially considering the management of complications. Further accumulation of the treatment experience would be desirable.

Ronen Sumagin ¹

Am J Pathol . 2024 Jan;194(1):2-12. doi: 10.1016/j.ajpath.2023.10.009. Epub 2023 Nov 2.

Neutrophils [polymorphonuclear leukocytes (PMNs)] execute important effector functions protecting the host against invading pathogens. However, their activity in tissue can exacerbate inflammation and inflammation-associated tissue injury and tumorigenesis. Until recently, PMNs were considered to be short-lived, terminally differentiated phagocytes. However, this view is rapidly changing with the emerging evidence of increased PMN lifespan in tissues, PMN plasticity, and phenotypic heterogeneity. Specialized PMN subsets have been identified in inflammation and in developing tumors, consistent with both beneficial and detrimental functions of PMNs in these conditions. Because PMN and tumor-associated neutrophil activity and the resulting beneficial/detrimental impacts primarily occur after homing to inflamed tissue/tumors, studying the underlying mechanisms of PMN/tumor-associated neutrophil trafficking is of high interest and clinical relevance. This review summarizes some of the key findings from over a decade of work from my laboratory and others on the regulation of PMN recruitment and identification of phenotypically and functionally diverse PMN subtypes as they pertain to gut inflammation and colon cancer.

Ang Cui ^1 2 3, Teddy Huang ⁴, Shuqiang Li ^5 4, Aileen Ma ^5 6, Jorge L Pérez ^5 6, Chris Sander ^5 7 8, Derin B Keskin ^5 4 9, Catherine J Wu ^5 9 10, Ernest Fraenkel ^5 11, Nir Hacohen ^12 13 14

Nature 2024 Jan;625(7994):377-384. doi: 10.1038/s41586-023-06816-9. Epub 2023 Dec 6.

Cytokines mediate cell-cell communication in the immune system and represent important therapeutic targets^1-3. A myriad of studies have highlighted their central role in immune function^4-13, yet we lack a global view of the cellular responses of each immune cell type to each cytokine. To address this gap, we created the Immune Dictionary, a compendium of single-cell transcriptomic profiles of more than 17 immune cell types in response to each of 86 cytokines (>1,400 cytokine-cell type combinations) in mouse lymph nodes in vivo. A cytokine-centric view of the dictionary revealed that most cytokines induce highly cell-type-specific responses. For example, the inflammatory cytokine interleukin-1β induces distinct gene programmes in almost every cell type. A cell-type-centric view of the dictionary identified more than 66 cytokine-driven cellular polarization states across immune cell types, including previously uncharacterized states such as an interleukin-18-induced polyfunctional natural killer cell state. Based on this dictionary, we developed companion software, Immune Response Enrichment Analysis, for assessing cytokine activities and immune cell polarization from gene expression data, and applied it to reveal cytokine networks in tumours following immune checkpoint blockade therapy. Our dictionary generates new hypotheses for cytokine functions, illuminates pleiotropic effects of cytokines, expands our knowledge of activation states of each immune cell type, and provides a framework to deduce the roles of specific cytokines and cell-cell communication networks in any immune response.

Motoki Yonekawa ^∗Akio Kawamura^∗Takashi Komai^†Tetsuzo Agishi^‡Masakazu Adachi^§ , https://doi.org/10.1016/0955-3886(96)00030-6

In cancer and rheumatoid arthritis, granulocytosis is often observed and indicates the progress of disease. We developed a granulocytapheresis system to permit granulocyte reduction. Cellulose acetate was found to be a selective and effective adsorbent. In an in vivo study using an acetate bead column, 9.2 × 10⁸ leukocytes were collected. Initially, granulocytapheresis was applied to terminal patients or those with stage IV cancer. Pain, cough and bloody sputum were reduced in spite of no decrease in the tumor size. Granulocytapheresis appears to prevent inflammatory damage in or around the tumor site. This granulocyte reduction technique was also applied to patients with rheumatoid arthritis. The Lansbury index markedly improved after treatment. As cytokines and adhesion molecules might contribute to symptoms, granulocytapheresis may be useful in improving the “Quality of Life” in these diseases.

https://www.sciencedirect.com/science/article/abs/pii/0955388696000306

T Tabuchi ¹, H Ubukata, S Sato, I Nakata, Y Goto, Y Watanabe, T Hashimoto, T Mizuta, M Adachi, T Soma, Anticancer Res
. May-Jun 1995;15(3):985-90.

We assessed the effect of granulocyte apheresis in patients exhibiting increased granulocyte-to-lymphocyte ratio in order to overcome granulocytosis occurring in the terminal stages of malignancies. 17 patients with post-operative recurrent metastatic tumors including 6 gastric, 3 colonic, 2 rectal, 1 esophageal and 5 breast cancers were selected. The granulocytapheresis was performed by extracorporeal vein-to-vein circulation equipped with an apheresis column filled with cellulose acetate beads. Each week the patients underwent one or two sessions of treatment that lasted 30 to 50 minutes per session at a flow rate of 30 to 50 ml/min. 15 sessions formed 1 therapeutic cycle. The effect of granulocytapheresis resulted in partial response (PR) in 4 cases, no change (NC) in 7 cases and partial disease (PD) in 6 cases. The performance status showed 30% remission. None of the patients exhibited significant side effects. Since the treatment demonstrated anti-tumor effects, granulocytapheresis may be applied during combined cancer treatments.

https://pubmed.ncbi.nlm.nih.gov/7645990/

K. Kukita,M. Yonekawa, H. Hirai,and M. Adachi A. Ikeda,M. Takahashi,J.Meguro, A.Kawamura, T. Mizuta, Jpn JApheresis13(2):148-149,1994

Immunological changes could be affected by this granulocyte/lymphocyte regulation system, but fixed tendencies were not observed within immunological parameters. Responses to this treatment changed on a case-by-case basis, Despite the improvement in subjective symptoms, tumor reduction was not observed. In addition to these immunological changes it has been suggested that this treatment may also have a positive effect on blood viscosity,

https://dl.ndl.go.jp/view/download/digidepo_10553072_po_ART0008042085.pdf?contentNo=1&alternativeNo=