Clinical Impact of Tumor-Infiltrating Lymphocytes in Esophageal Squamous Cell Carcinoma.

BACKGROUND: Recently, several immune checkpoint inhibitors have been developed and are being used to treat malignant melanoma, lung cancer, and other cancers. Several reports have indicated that tumor-infiltrating lymphocytes (TILs) are associated with clinical and histopathologic risk factors in various cancers. However, the role of TILs in esophageal squamous cell carcinoma (ESCC) has not been well studied. This study aimed to investigate the perilesional status of TILs in ESCC and to show associations between TILs and clinical variables. METHODS: The study enrolled 277 ESCC patients. Evaluation of TILs was performed according to the criteria of the International TILs Working Group 2014, and associations between TIL and clinicopathologic variables were examined. RESULTS: Most of the clinicopathologic factors were not statistically associated with TIL status. The number of patients who received adjuvant therapy was significantly larger in the TIL-negative group. Cancer-specific survival (CSS) of patients in the TIL-positive group was significantly better than in the TIL-negative group. Among the patients who received adjuvant therapy, CSS was significantly better in the TIL-positive group than in the TIL-negative group. Uni- and multivariate analyses identified tumor depth and TIL status as independent prognostic factors for CSS. Among the other clinicopathologic variables, TIL status was the strongest CSS indicator. CONCLUSION: Tumor-infiltrating lymphocyte status is a strong predictor of good prognosis for ESCC patients.

Diversity and shared T-cell receptor repertoire analysis in esophageal squamous cell carcinoma.

The tumor immune response is dependent on the interaction between tumor cells and the T-cell subset expressing the T-cell receptor (TCR) repertoire that infiltrates into the tumor microenvironment. The present study explored the diversity and shared TCR repertoires expressed on the surface of locoregional T cells and identified the T lymphocyte subsets infiltrating into esophageal squamous cell carcinoma (ESCC), in order to provide insight into the efficiency of immunotherapy and the development of a novel immune-oriented therapeutic strategy. A total of 53 patients with ESCC were enrolled in the present study, and immunohistochemical analysis of CD3, CD8, CD45RO, FOXP3, CD274, HLA class I and AE1/AE3 was performed. Digital pathological assessment was performed to evaluate the expression level of each marker. The clinicopathological significance of the immuno relation high (IR-Hi) group was assessed. Adaptor ligation PCR and next-generation sequencing were performed to explore the diversity of the TCR repertoire and to investigate the shared TCR repertoire in the IR-Hi group. Repertoire dissimilarity index (RDI) analysis was performed to assess the diversity of TCR, and the existence of shared TCRα and TCRß was also investigated. Further stratification was performed according to the expression of markers of different T-cell subsets. Patients were stratified into IR-Hi and immuno relation low (IR-Lo) groups. Cancer-specific survival and recurrence-free survival rates were significantly improved in the IR-Hi group compared with in the IT-Lo group. The diversity of the TCR repertoire was significantly higher in the IR-Hi group. TCR repertoire analysis revealed 27 combinations of TCRα and 23 combinations of TCRß VJ regions that were shared among the IR-Hi group. The IR-Hi group was divided into three clusters. Overall, the current findings revealed that the IR-Hi group maintained the diversity of TCR, and a portion of the IR-Hi cases held the T cells with shared TCR repertoires, implying recognition of shared antigens. The prognosis of patients with ESCC was affected by the existence of immune response cells and may possibly be stratified by the T-cell subsets.

Successful Resection of a Large Rectal Adenoma Using the Transsacral Approach.

The transsacral approach is not routinely used for treating rectal tumors. We report the case of a 65-year-old man with a large adenoma at the posterior wall of the mid-rectum who was treated via the transsacral approach. The same lesion had been treated using transsacral endoscopic microsurgery 8 years previously. Moreover, 11 years previously he had undergone a laparotomy for bladder cancer, and an Indiana pouch had been constructed. Abdominal computed tomography showed that the pouch was adjacent to the rectum. Therefore, the less-invasive transsacral approach, rather than the transabdominal approach, was chosen for treatment. The lesion was successfully resected, without disturbing the pouch. Histological analysis indicated tubular adenoma, with a small focus of intramucosal adenocarcinoma, and negative margins. Thus, we achieved successful resection of mid-rectal lesions via the transsacral approach, without the morbidity associated with major laparotomy. We suggest that this procedure should be a part of a surgeon's armamentarium.