Prognostic relevance of tumor‐resident memory T cells in metastatic lymph nodes of esophageal squamous cell carcinoma

Abstract

Tumor‐resident memory T (T RM ) cells in primary tumors are reportedly associated with a favorable prognosis in several malignancies. However, the behaviors and functions of T RM cells in regional lymph nodes (LNs) of esophageal cancer remain poorly understood. The aim of this study was to elucidate the effects of T RM cells in regional LNs of esophageal cancer on clinicopathological findings and prognosis. Specimens of esophageal cancer and primary metastatic LNs (recurrent nerve LNs) were obtained from 84 patients who underwent radical esophagectomy between 2011 and 2017. We performed immunohistochemistry to enumerate and analyze T RM cells, and used flow cytometry to investigate the function of T RM cells. T RM cells were observed in both metastatic LNs and primary tumors. T RM cell‐rich specimens exhibited reduced lymphatic invasion and LN metastasis and prolonged survival compared with T RM cell‐poor specimens. T RM cells in metastatic LNs were more significantly associated with enhanced survival than T RM cells in primary tumors. T RM cells expressed high levels of granzyme B as a cytotoxicity marker. Our results suggested that high T RM cell infiltration in metastatic LNs improves survival even though LN metastasis is commonly associated with poor prognosis. T RM cells possibly contribute to antitumor immunity in regional LNs.

Usefulness of Biopsy Specimens for Evaluating CD103+Tumor-resident Memory T Cells in Esophageal Cancer

“…The preoperative regimens consisted of two cycles of 5-fluorouracil+cisplatin (FP), 5-fluorouracil+nedaplatin (FGP), or docetaxel+cisplatin+5-fluorouracil (DCF). The regimen schedules have been reported previously (7). FP consisted of a four-week cycle of 5-fluorouracil at 800 mg/m 2 body surface area on days one through five and cisplatin at 80 mg/m 2 on day one.…”

“…Interestingly, we previously suggested that T RM in esophageal cancer is associated with the response to ICIs. Other studies have also reported that T RM has potential in the ICI treatment of gastrointestinal tumors (7,8). The evaluation of T RM is possibly instrumental, even for ICI treatment.…”

“…T RM have attracted attention for their anti-tumor function and association with the effectiveness of immune checkpoint inhibitors (ICIs). We previously investigated T RM infiltration in esophageal cancer (7). Esophageal cancer is one of the worst cancers with regard to prognosis, but we reported that T RM -rich patients exhibit a better prognosis and have fewer lymph node metastasis than T RM -poor patients (7).…”

“…We previously investigated T RM infiltration in esophageal cancer (7). Esophageal cancer is one of the worst cancers with regard to prognosis, but we reported that T RM -rich patients exhibit a better prognosis and have fewer lymph node metastasis than T RM -poor patients (7). Additionally, the emergence of ICIs has provided more treatment options for unresectable progressive, or recurrent esophageal cancer.…”

45-Color Full Spectrum Flow Cytometry Panel for Deep Immunophenotyping of the Major Lineages Present in Human Peripheral Blood Mononuclear Cells with Emphasis on the T cell Memory Compartment

“…CD103 is expressed by intraepithelial lymphocytes (αβ and γδ T cells), lamina propria T cells, regulatory T cells, and a subset of DCs. The presence of CD103 + resident memory T cells has been linked to better survival upon treatment in patients with head and neck squamous cell carcinoma [24] and esophageal cancer [42]. For example, Gattas G et al demonstrated that the presence of CD103 + CDS + tumor-infiltrating lymphocytes is associated with better responses to chemoimmunotherapy in patients with head and neck squamous cell carcinoma [43].…”