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Biomarkers for the Immune Checkpoint Inhibitors
Published in Sherry X. Yang, Janet E. Dancey, Handbook of Therapeutic Biomarkers in Cancer, 2021
Weijie Ma, Sixi Wei, Eddie C. Tian, Tianhong Li
HLA typing has been identified as a predictive biomarker in novel immunotherapies to guide treatment. HLA-DR expression strongly correlates with response to anti-PD-1. MHC-II positivity on tumor cells is associated with therapeutic response, progression-free and overall survival, as well as CD4+ and CD8+ tumor infiltrates [76]. Host germline genetics also affects response to ICIs in NSCLC and other tumor types. Maximal heterozygosity at HLA-I loci (A, B, and C) improves overall survival after immunotherapy compared to patients who are homozygous for at least one HLA locus. In two independent cancer cohorts, patients with the HLA-B44 supertype had extended survival, whereas the HLA-B62 supertype (including HLA-B*15:01) or somatic LOH at HLA-I, was associated with poor outcome. Molecular dynamics simulations of HLA-B*15:01 have revealed unique elements that may impair CD8+ T cell recognition of neoantigens [77].
Individualized management of cytomegalovirus in solid organ transplant recipients
Published in Expert Review of Precision Medicine and Drug Development, 2021
Huma Saeed, Matthew Thoendel, Raymund R Razonable
Allograft recipients with human leukocyte antigen (HLA)-B7 positive donors and those with HLA B44 alleles are at an increased risk of CMV infection and disease [52,53]. Genetic polymorphisms in certain host genes such as programmed death-1.3 A allele confers increased risk of CMV infection in renal transplant recipients who are not receiving antiviral prophylaxis [54]. Additionally, studies have demonstrated genetic polymorphisms in the newly described Type-III interferons, IFN-λ and IFNL, especially IFNL3 and IFNL4 impact the replication of various viruses, including CMV, due to its direct effect on innate and adaptive immunity as well as direct antiviral functions [55]. A higher incidence of CMV replication has been reported in hosts carrying polymorphism in the IFNL3/4 region, especially among those who were not receiving antiviral prophylaxis [56].
Immune checkpoint inhibitors: a new era for esophageal cancer
Published in Expert Review of Anticancer Therapy, 2019
Li-Qing Zou, Xi Yang, Yi-Da Li, Zheng-Fei Zhu
Heterozygosity and certain superfamilies of human leukocyte antigen (HLA) could also influence response to ICIs. Recently, an analysis [20] of the HLA class 1 genotypes in 1,535 patients with advanced malignancies (mostly melanoma or non-small-cell lung cancer) revealed statistically significant associations between HLA homozygosity and ICI treatment outcomes. Additionally, they also found that certain HLA superfamilies were associated with an exceptional response, such as HLA B44. Evidence has shown that in EC HLA may also reflect the immune status and help to predict treatment outcome. Joshi N et al. [21] examined the molecular profiles associated with regression and progression of dysplastic lesions in normal esophageal mucosa from 29 individuals, a subset of the esophageal squamous dysplasia cohort. The result showed individuals whose lesions regressed after chemoprevention had higher expression of genes associated with immune stimulation, HLA-DRA, HLA-DPA1, HLA-DBQ1 included. Sumiyoshi K et al. [22] examined HLA-DR in normal esophageal epithelium, dysplasia, intraepithelial carcinomas, and invasive carcinomas. HLA-DR antigen was expressed in 2 of the 625 specimens of non-cancerous squamous epithelium (0.3%), 21 of the 50 areas of dysplasia (42.0%), 23 of the 38 intraepithelial carcinomas (60.5%), and 12 of the 35 invasive carcinomas (34.4%). They also found, at different sites, T-cell infiltration positively correlated with HLA-DR expression (P < 0.01). These facts support the idea that HLA profile has the potential to reflect local immune response in EC patients.
Remission with tocilizumab in a patient with erosive hand osteoarthritis
Published in Scandinavian Journal of Rheumatology, 2021
M Kondo, Y Murakawa, M Honda, M Moriyama
A 59-year-old Japanese woman had noticed that the distal interphalangeal (DIP) joint deformed gradually from two years ago. Finger arthralgia at the DIP and proximal interphalangeal (PIP) joints appeared and worsened gradually. She could not sleep at night because of severe arthralgia. On presentation, Heberden’s and Bouchard’s nodes were present. She had been treated for right breast cancer, but had no history of psoriasis. There was no family history of rheumatoid arthritis, OA, or psoriasis. Laboratory tests revealed slightly high C-reactive protein (0.62 mg/dL, normal < 0.14), and matrix metalloproteinase-3 (61.8 ng/mL, normal 20.9–50.6) levels, and a moderately elevated erythrocyte sedimentation rate (33 mm/h, normal 3–15). Rheumatoid factor and anti-cyclic citrullinated peptide antibody were negative. While the serum tumour necrosis factor (TNF)-α level was not elevated, IL-6 was high at 3.28 (normal < 2.41) pg/mL. Plain X-rays revealed sawtooth and gull-wing erosions of the PIP and DIP joints (Figure 1A). Ultrasonography (US) revealed synovial swelling and a Doppler signals in the swollen joints (Figure 1B). HLA typing showed the presence of the HLA-B44 allele, which is frequently associated with EHOA (1). We diagnosed EHOA and treated her with non-steroidal anti-inflammatory drugs, which were ineffective. Therefore, we started TCZ (via subcutaneous injection, 162 mg biweekly) and her arthralgia improved gradually (Figure 2). Six months later, her tender and swollen joint counts had improved from 8 to 4 and 8 to 2, respectively. Her visual analogue scale for pain also improved, from 64 to 15 (mm). The synovial swelling and Doppler signals on US improved remarkably (Figure 1B).