Publications by authors named "Keisuke Shirai"

Article Synopsis
  • This study explores blood biomarkers that can predict responses to immune checkpoint inhibitors (ICIs) for patients with recurrent/metastatic head and neck squamous cell carcinoma, addressing challenges like tumor sample variability.
  • Researchers enrolled 100 patients and analyzed blood immune profiles, focusing on factors like tumor mutational burden (TMB) and PD-L1 scores, with a goal to find associations with treatment outcomes.
  • Key findings revealed that high levels of neutrophils and monocytes were linked to worse survival, while higher CD4T cells correlated with better outcomes, highlighting the potential of using blood tests for predicting ICI treatment responses.
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Background: Overcoming immune suppression is a major barrier to eliciting potent CD8 T cell responses against cancer. Treatment with anti-CD4 monoclonal antibody is an effective means for eliminating CD4Foxp3 regulatory (Treg) cells in preclinical models and has also demonstrated efficacy in early clinical trials. However, the underlying basis for treatment efficacy, more specifically the implications of codepleting other CD4-expressing cell compartments in tumor-bearing hosts, is not well understood.

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Background: Combination immune checkpoint blockade targeting PD-1 and CTLA-4 leads to high response rates and improved survival in advanced cutaneous melanoma (CM). Less is known about the efficacy of this combination in acral lentiginous melanoma (ALM).

Objectives: To determine the efficacy of combination immune checkpoint blockade targeting PD-1 and CTLA-4 in a real-world, diverse population of ALM.

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Background: Meconium peritonitis is a noninfectious chemical peritonitis that occurs following fetal intestinal perforation and leakage of meconium into the abdominal cavity. Because of the lack of appropriate animal models, its pathophysiology has not yet been elucidated. We aimed to create a neonatal mouse model of meconium peritonitis using human meconium slurry (MS).

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The ecto-ATPase CD39 is expressed on exhausted CD8+ T cells in chronic viral infection and has been proposed as a marker of tumor-specific CD8+ T cells in cancer, but the role of CD39 in an effector and memory T cell response has not been clearly defined. We report that CD39 is expressed on Ag-specific CD8+ short-lived effector cells, while it's co-ectoenzyme, CD73, is found on memory precursor effector cells (MPECs) in vivo. Inhibition of CD39 enzymatic activity during in vitro T cell priming enhances MPEC differentiation in vivo after transfer and infection.

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This study examined whey protein's impact on insulin resistance in a high-fat diet-induced pediatric obesity mouse model. Pregnant mice were fed high-fat diets, and male pups continued this diet until 8 weeks old, then were split into high-fat, whey, and casein diet groups. At 12 weeks old, their body weight, fasting blood glucose (FBG), blood insulin level (IRI), homeostatic model assessment for insulin resistance (HOMA-IR), liver lipid metabolism gene expression, and liver metabolites were compared.

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This study addresses the challenge of predicting the response of head and neck squamous cell carcinoma (HNSCC) patients to immunotherapy. Using DNA methylation cytometry, we analyzed the immune profiles of six HNSCC patients who showed a positive response to immunotherapy over a year without disease progression. There was an initial increase in CD8 T memory cells and natural killer cells during the first four cycles of immunotherapy, which then returned to baseline levels after a year.

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Introduction: Food desert (FD) residence has emerged as a risk factor for poor outcomes in breast, colon and esophageal cancers. The purpose of this retrospective study was to examine FD residence as an associated risk factor in nonsmall cell lung cancer (NSCLC) patients treated with anatomic lung resection (ALR).

Methods: All consecutive ALRs for stage I-III NSCLC from January 2015 to December 2017 at a single institution were reviewed.

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The ecto-ATPase CD39 is expressed on exhausted CD8+ T cells in chronic viral infection and has been proposed as a marker of tumor-specific CD8+ T cells in cancer, but the role of CD39 in an effector and memory T cell response has not been clearly defined. We report that CD39 is expressed on antigen-specific CD8+ short-lived effector cells (SLECs), while it's co-ecto-enzyme, CD73, is found on memory precursor effector cells (MPEC) . Inhibition of CD39 enzymatic activity during T cell priming enhances MPEC differentiation after transfer and infection.

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BACKGROUND Early therapies for metastatic melanoma improved patient quality of life; however, median survival remained unaffected. Studies are showing that surgical excision with the combination of immune checkpoint inhibitor (ICI) therapy has better outcomes than systemic therapy alone. This single-center case series describes 7 patients with oligometastatic melanoma treated by metastasectomy in combination with ICI and BRAF inhibitors.

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Since the first approval for immune checkpoint inhibitors (ICIs) for the treatment of cutaneous melanoma more than a decade ago, immunotherapy has completely transformed the treatment landscape of this chemotherapy-resistant disease. Combination regimens including ICIs directed against programmed cell death protein 1 (PD-1) with anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) agents or, more recently, anti-lymphocyte-activation gene 3 (LAG-3) agents, have gained regulatory approvals for the treatment of metastatic cutaneous melanoma, with long-term follow-up data suggesting the possibility of cure for some patients with advanced disease. In the resectable setting, adjuvant ICIs prolong recurrence-free survival, and neoadjuvant strategies are an active area of investigation.

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Pembrolizumab and ipilimumab/nivolumab (ipi/nivo) combination are FDA-approved immune checkpoint inhibitor (ICI) therapies for metastatic melanoma. ICIs could result in various inflammation responses known as immune-related adverse events (IRAEs). We report a patient with metastatic melanoma who developed multiple IRAEs including sarcoidosis-like reaction (SLR), diabetic ketoacidosis (DKA), and worsening hypothyroidism on ICIs.

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Background: The usage of immunotherapy to treat skin malignancies in transplant patients requires weighing the risk of acute organ transplant rejection with the potential reduction of antitumor efficacy by transplant immunosuppression. Reducing the duration of immune checkpoint inhibitor treatment may help prevent acute transplant rejection and late immune-related adverse events.

Case Presentation: An allogenic kidney transplant patient who developed regionally metastatic cutaneous squamous cell carcinoma received four cycles of pembrolizumab with complete response to therapy.

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The anti-PD-1 antibody cemiplimab has demonstrated effectiveness in the setting of locally advanced basal cell carcinoma (BCC) and squamous cell carcinoma. We describe a case of a large, locally invasive basosquamous carcinoma, an aggressive type of BCC, invading the left sternocleidomastoid muscle with near compression of the left internal jugular vein producing a severe anaemia secondary to ulceration and chronic blood loss. The patient was initially started on vismodegib monotherapy but failed to respond.

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Background: The coronavirus disease 2019 outbreak has prompted some hospitals to implement screening tests upon admission since 2020. FilmArray® Respiratory 2.1 Panel (FilmArray) is a multiplex polymerase chain reaction (PCR) test with high sensitivity and specificity for detecting respiratory pathogens.

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Background: Basal cell carcinoma (BCC) is the most common malignancy worldwide, yet the management of patients with advanced or metastatic disease is challenging, with limited treatment options. Recently, programmed death receptor 1 (PD-1) inhibition has demonstrated activity in BCC after prior Hedgehog inhibitor treatment.

Methods: We conducted a multicenter, retrospective analysis of BCC patients treated with PD-1 inhibitor therapy.

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Article Synopsis
  • - The article summarizes insights from the "US-Japan Conference on Advances in Oncology: Cancer and Infectious Diseases" held online on June 25, 2021.
  • - It focuses on the relationships between cancer research and infectious diseases, highlighting recent advancements in both basic science and clinical trials.
  • - The review emphasizes the importance of interdisciplinary collaboration and the need for ongoing research in understanding how infections may influence cancer outcomes and treatment strategies.
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Background: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of non-small-cell lung cancer (NSCLC). Denosumab is a humanized monoclonal antibody to RANK ligand used to prevent skeletal-related events of bone metastases in solid tumors. We are reporting the clinical outcomes in our NSCLC patients who received RANKL inhibitor in combination with ICIs.

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The nature of the anti-tumor immune response changes as primary tumors progress and metastasize. We investigated the role of resident memory (Trm) and circulating memory (Tcirm) cells in anti-tumor responses at metastatic locations using a mouse model of melanoma-associated vitiligo. We found that the transcriptional characteristics of tumor-specific CD8 T cells were defined by the tissue of occupancy.

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Mucosal melanoma is a rare subtype of melanoma and represents a unique diagnosis and treatment challenge. Immune-checkpoint inhibitors (ICIs) have revolutionised metastatic melanoma treatment, and one of the leading regimens is the combination of ipilimumab (anti-cytotoxic T lymphocyte-associated antigen 4: CTLA4) and nivolumab (anti-programmed cell death protein 1: PD1). We report a case of a patient with metastatic mucosal melanoma treated with ipilimumab and nivolumab who developed multiple immune-related adverse events (irAEs) including uveitis, type I diabetes complicated by diabetic ketoacidosis, destructive thyroiditis, hepatitis and vitiligo.

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While T-cell responses to cancer immunotherapy have been avidly studied, long-lived memory has been poorly characterized. In a cohort of metastatic melanoma survivors with exceptional responses to immunotherapy, we probed memory CD8 T-cell responses across tissues, and across several years. Single-cell RNA sequencing revealed three subsets of resident memory T (T) cells shared between tumors and distant vitiligo-affected skin.

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Inflammatory myofibroblastic tumor (IMT) is a distinctive fibroblastic and myofibroblastic spindle cell neoplasm with an accompanying inflammatory cell infiltrate and frequent receptor tyrosine kinase activation at the molecular level. The tumor may recur and rarely metastasizes. IMT is rare in the head and neck region, and limited information is available about its clinicopathologic and molecular characteristics in these subsites.

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Immune checkpoint inhibitors (ICIs) are widely used for various malignancies. However, their safety and efficacy in patients with a kidney transplant have not been defined. To delineate this, we conducted a multicenter retrospective study of 69 patients with a kidney transplant receiving ICIs between January 2010 and May 2020.

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Background: Biomarkers predicting immunotherapy response in metastatic renal cell cancer (mRCC) are lacking. PD-L1 immunohistochemistry is a complementary diagnostic for immune checkpoint inhibitors (ICIs) in mRCC, but has shown minimal clinical utility and is not used in routine clinical practice.

Methods: Tumor specimens from 56 patients with mRCC who received nivolumab were evaluated for PD-L1, cell proliferation (targeted RNA-seq), and outcome.

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Introduction: Almonertinib (HS-10296) is a novel, third-generation EGFR tyrosine kinase inhibitor (EGFR TKI) that targets both EGFR-sensitizing and T790M resistance mutations. This first-in-human trial aimed to evaluate the safety, efficacy, and pharmacokinetics of almonertinib in patients with locally advanced or metastatic EGFR mutation-positive NSCLC that had progressed after pevious EGFR TKI therapy.

Methods: This phase 1, open-label, multicenter clinical trial (NCT0298110) included dose-escalation (55, 110, 220, and 260 mg) and dose-expansion cohorts (55, 110, and 220 mg) with once daily oral administration of almonertinib.

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