Tsuyoshi Saito

Step-by-step demonstration of “sciatic-nerve-preserved beyond-LEER” in a Thiel-embalmed cadaver: a novel salvage surgery for recurrent gynecologic malignancies

Identification of immunogenic HLA class I and II neoantigens using surrogate immunopeptidomes

Neoantigens arising from somatic mutations are tumor specific and induce antitumor host T cell responses. However, their sequences are individual specific and need to be identified for each patient for therapeutic applications. Here, we present a proteogenomic approach for neoantigen identification, named Neoantigen Selection using a Surrogate Immunopeptidome (NESSIE). This approach uses an autologous wild-type immunopeptidome as a surrogate for the tumor immunopeptidome and allows human leukocyte antigen (HLA)–agnostic identification of both HLA class I (HLA-I) and HLA class II (HLA-II) neoantigens. We demonstrate the direct identification of highly immunogenic HLA-I and HLA-II neoantigens using NESSIE in patients with colorectal cancer and endometrial cancer. Fresh or frozen tumor samples are not required for analysis, making it applicable to many patients in clinical settings. We also demonstrate tumor prevention by vaccination with selected neoantigens in a preclinical mouse model. This approach may benefit personalized T cell–mediated immunotherapies.

Early outcomes of three new robotic surgical systems in patients undergoing hysterectomy

New robot models, such as hinotori

Relationship between the lateral dissection lines of various radical hysterectomies and anatomical structures in the female pelvis: an educational video from the Sapporo Cadaver Surgical Workshop

Radical hysterectomy with pelvic lymph node dissection is the treatment of choice for cervical cancer. All gynecologic oncologists should master this technique. The surgical procedure requires a wide dissection of the female pelvis. Performing radical hysterectomy without a thorough knowledge of the anatomy of the female pelvis can lead to serious complications. For novice surgeons to safely perform radical hysterectomy, mastering the 3-dimensional anatomy of the pelvis and aligning the dissection lines of radical hysterectomy to the female pelvic anatomy is crucial. Educational materials that demonstrate the anatomical relationship between dissection lines in radical hysterectomy and the surrounding pelvic structures are lacking. We aimed to create educational material to overcome these problems. Laparoscopic nerve sparing, non-nerve sparing, and super-radical hysterectomies, exposing pivotal pelvic anatomical structures, were performed on a Thiel-embalmed cadaver. Nerve sparing, non-nerve sparing, and super-radical hysterectomies were laparoscopically performed in the right hemi-pelvis of the cadaver. We exposed the external and internal iliac vessels; obturator, sciatic, femoral, hypogastric, and pelvic splanchnic nerves and the pelvic nerve plexus; internal obturator, piriform, and coccygeal muscles; sacrospinous ligament; and ischial spine. Thus, we demonstrated where the dissection lines of the various radical hysterectomies are in a female pelvis. Using a Thiel-embalmed cadaver, we demonstrated the relationship between the dissection lines of various radical hysterectomies and pivotal sidewall anatomical structures in a female pelvis. The anatomical detail shown in the video captured during this procedure may assist surgeons to safely perform various radical hysterectomies.

Identification and Phenotypic Characterization of Neoantigen-Specific Cytotoxic CD4+ T Cells in Endometrial Cancer

Abstract Tumor-reactive CD4+ T cells often accumulate in the tumor microenvironment (TME) in human cancer, but their functions and roles in antitumor responses remain elusive. Here, we investigated the immunopeptidome of HLA class II–positive (HLA-II+) endometrial cancer with an inflamed TME using a proteogenomic approach. We identified HLA-II neoantigens, one of which induced polyclonal CD4+ tumor-infiltrating lymphocyte responses. We then experimentally demonstrated that neoantigen-specific CD4+ tumor-infiltrating lymphocytes lyse target cells in an HLA-II–dependent manner. Single-cell transcriptomic analysis of the TME coupled with T-cell receptor sequencing revealed the presence of CD4+ T-cell clusters characterized by CXCL13 expression. The CXCL13+ clusters contained two subclusters with distinct cytotoxic gene expression patterns. The identified neoantigen-specific CD4+ T cells were found exclusively in one of the CXCL13+ subclusters characterized by granzyme B and CCL5 expression. These results demonstrate the involvement of tumor-reactive CD4+ T cells with cytotoxic function in immune surveillance of endometrial cancer and reveal their transcriptomic signature.