Tissue and circulating PD-L2: moving from health and immune-mediated diseases to head and neck oncology

Muraro, Elena; Romanò, Rebecca; Fanetti, Giuseppe; Vaccher, Emanuela; Turturici, Irene; Lupato, Valentina; Torre, Fabio Biagio La; Polesel, Jerry; Fratta, Elisabetta; Giacomarra, Vittorio; Franchin, Giovanni; Steffan, Agostino; Spina, Michele; Alfieri, Salvatore

doi:10.1016/j.critrevonc.2022.103707

Cited by 15 publications

(9 citation statements)

References 110 publications

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“…LAG-3 can block the exhaustion of T and B cells and even enhance the activity and proportion of CD8+ T cells. 55,56 Consistent with the fact that positive immune response activation often coexists with negative immune response regulation activation, 57 the negative immune regulation pattern (EFA Factor 2, represented by galectin-9, 58,59 TGF-β, 60,61 and PD-L2 62,63 ) was also observed to be activated.…”

Section: Exploratory Factor Analysis Of Soluble Costimulatory Moleculesmentioning

confidence: 59%

Immune Regulation Patterns in Response to Environmental Pollutant Chromate Exposure-Related Genetic Damage: A Cross-Sectional Study Applying Machine Learning Methods

Su,

Zhang,

Hong

et al. 2024

Environ. Sci. Technol.

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Exposure to hexavalent chromium damages genetic materials like DNA and chromosomes, further elevating cancer risk, yet research rarely focuses on related immunological mechanisms, which play an important role in the occurrence and development of cancer. We investigated the association between blood chromium (Cr) levels and genetic damage biomarkers as well as the immune regulatory mechanism involved, such as costimulatory molecules, in 120 workers exposed to chromates. Higher blood Cr levels were linearly correlated with higher genetic damage, reflected by urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) and blood micronucleus frequency (MNF). Exploratory factor analysis revealed that both positive and negative immune regulation patterns were positively associated with blood Cr. Specifically, higher levels of programmed cell death protein 1 (PD-1; mediated proportion: 4.12%), programmed cell death ligand 1 (PD-L1; 5.22%), lymphocyte activation gene 3 (LAG-3; 2.11%), and their constitutive positive immune regulation pattern (5.86%) indirectly positively influenced the relationship between blood Cr and urinary 8-OHdG. NOD-like receptor family pyrin domain containing 3 (NLRP3) positively affected the association between blood Cr levels and inflammatory immunity. This study, using machine learning, investigated immune regulation and its potential role in chromate-induced genetic damage, providing insights into complex relationships and emphasizing the need for further research.

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Section: Exploratory Factor Analysis Of Soluble Costimulatory Moleculesmentioning

confidence: 59%

Immune Regulation Patterns in Response to Environmental Pollutant Chromate Exposure-Related Genetic Damage: A Cross-Sectional Study Applying Machine Learning Methods

Su,

Zhang,

Hong

et al. 2024

Environ. Sci. Technol.

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“…Our pooled results also suggested that PD‐L1 inhibitors monotherapy had significantly lower incidences of any grade trAEs, grade three or more trAEs, and trAEs leading to discontinuation of treatment compared with both PD‐1 inhibitors monotherapy and ICIs combination therapy. In addition to PD‐L1, PD‐L2 was described as a second ligand for PD‐1 with overlapping functions 34 . PD‐L2 expression in tumor cells was found to be more common in HNSCC samples compared with some other cancer types such as renal cell carcinoma and melanoma 35 .…”

Section: Discussionmentioning

confidence: 99%

“…In addition to PD-L1, PD-L2 was described as a second ligand for PD-1 with overlapping functions. 34 PD-L2 expression in tumor cells was found to be more common in HNSCC samples compared with some other cancer types such as renal cell carcinoma and melanoma. 35 Therefore, the incomplete blocking of checkpoint signaling due to the high prevalence of PD-L2 expression in HNSCC might be one of the reasons for the lower toxicity of PD-L1 inhibitors.…”

Section: Populationmentioning

confidence: 94%

Toxicity profiles of immune checkpoint inhibitors for recurrent or metastatic head and neck squamous cell carcinoma: A systematic review and meta‐analysis

Dang,

Li,

Liu

et al. 2024

Cancer Medicine

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BackgroundImmune checkpoint inhibitors (ICIs) are widely used in recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC); however, the toxicity profiles are inconclusive.MethodsClinical trials evaluating ICIs for R/M HNSCC were searched from online databases. The characteristics of the studies and the results of incidences of any grade treatment‐related adverse events (trAEs), grade three or more trAEs, treatment‐related deaths, trAEs leading to discontinuation of treatment, and specific trAEs were extracted.ResultsTwenty studies with 3756 patients were included. The pooled incidences of any grade trAEs, grade three or more trAEs, treatment‐related deaths, trAEs leading to discontinuation of treatment for overall population were 62.07% (95% CI, 59.07%–65.02%), 13.82% (95% CI, 11.23%–16.62%), 0.39% (95% CI, 0.15%–0.71%), 3.99% (95% CI, 2.36%–5.95%), respectively. Programmed cell death protein 1 (PD‐1) inhibitors monotherapy and ICIs combination therapy had significantly higher incidences of any grade trAEs (odds ratio [OR], 1.25, 95% CI, 1.05–1.49 and 1.36, 95% CI, 1.15–1.60, respectively), grade three or more trAEs (OR, 1.41, 95% CI, 1.08–1.84 and 1.79, 95% CI, 1.39–2.30, respectively), trAEs leading to discontinuation of treatment (OR, 3.98, 95% CI, 2.06–7.70 and 10.14, 95% CI, 5.49–18.70, respectively) compared with programmed death‐ligand 1 (PD‐L1) inhibitors monotherapy. ICIs combination therapy had a significantly higher incidence of grade three or more trAEs compared with PD‐1 inhibitors monotherapy (OR, 1.27, 95% CI, 1.03–1.55); however, the incidences of any grade trAEs and trAEs leading to discontinuation of treatment were not significant different.ConclusionsOur study suggests that the incidences of grade three or more trAEs, treatment‐related deaths, and trAEs leading to discontinuation of treatment are low in R/M HNSCC patients treated with ICIs. PD‐L1 inhibitors monotherapy may be safer compared with PD‐1 inhibitors monotherapy and ICIs combination therapy.

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“…sPD-L2 has also been described though its biological function and is even more poorly understood [ 18 ]. Low levels of sPD-L2 have been associated with systemic lupus erythematosus development compared with healthy controls, and low levels have also been associated with platinum resistance in ovarian cancer [ 19 , 20 ].…”

Section: Systemic Sclerosis/sclerodermamentioning

confidence: 99%

Checkpoint Inhibitor-Associated Scleroderma and Scleroderma Mimics

et al. 2023

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Immune checkpoint inhibitors (ICI) are the standard of care for various malignancies and have been associated with a wide spectrum of complications that are phenotypically akin to primary autoimmune diseases. While the literature on these toxicities is growing, there is a paucity of data regarding ICI-associated scleroderma which can carry significant morbidity and limit the ability to continue effective ICI therapy. Our review aimed to analyze the current literature on ICI-associated systemic scleroderma (ICI-SSc) and key scleroderma mimics. Cases of ICI-SSc had notable differences from primary SSc, such as fewer vascular features and less seropositivity (such as scleroderma-specific antibodies and antinuclear antibodies). We found that patients with a diagnosis of SSc prior to the start of ICI can also experience flares of pre-existing disease after ICI treatment used for their cancer. Regarding scleroderma mimics, several cases of ICI-eosinophilic fasciitis have also been described with variable clinical presentations and courses. We found no cases of scleroderma mimics: ICI-scleromyxedema or ICI-scleroedema. There is a critical need for multi-institutional efforts to collaborate on developing a patient database and conducting robust, prospective research on ICI-scleroderma. This will ultimately facilitate more effective clinical evaluations and management for ICI-scleroderma.

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Tissue and circulating PD-L2: moving from health and immune-mediated diseases to head and neck oncology

Cited by 15 publications

References 110 publications

Immune Regulation Patterns in Response to Environmental Pollutant Chromate Exposure-Related Genetic Damage: A Cross-Sectional Study Applying Machine Learning Methods

Immune Regulation Patterns in Response to Environmental Pollutant Chromate Exposure-Related Genetic Damage: A Cross-Sectional Study Applying Machine Learning Methods

Toxicity profiles of immune checkpoint inhibitors for recurrent or metastatic head and neck squamous cell carcinoma: A systematic review and meta‐analysis

Checkpoint Inhibitor-Associated Scleroderma and Scleroderma Mimics

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