Prognostic Value of Tissue-Resident Memory T Cells and Tumor Microenvironmental Features in Resected Pancreatic Adenocarcinoma

Abstract

Background: Pancreatic ductal adenocarcinoma differs from other solid tumors with its unique immunosuppressive microenvironment and non-immunogenic feature. There are not many studies in the literature investigating the effect of these features on prognosis. Aims: To investigate the prognostic value of tissue-resident memory T cells, tumor microenvironment features, and tumor-associated immune cells in resected pancreatic ductal adenocarcinomas. Study Design: Retrospective cross-sectional study. Methods: Of 138 patients diagnosed with pancreatic ductal adenocarcinoma between 2011 and 2018, 81 were included in the study. Specimens from operated patients were reassessed separately as peritumoral and intratumoral areas for tissue resident memory cells and tumor microenvironmental elements (tumor infiltrating lymphocytes, tumor stroma, CD204+ macrophages, PDL1+ immune cells). Disease-free survival and overall survival were defined from the date of operation to the date of recurrence and the date of first diagnosis to the date of death, respectively. If the patient was alive, the last visit date was taken into account. Results: The median age at diagnosis was 63 (range: 40-78). The median follow-up period was 18.9 months (range: 1.4-80.4 months). Median overall survival was 23.7 months (1.4-80.4 months) and median disease-free survival was 10.8 months (1.4-74.4 months). Patients with higher intra-tumoral tissue-resident memory cell counts had a longer survival trend than those having lower values (25.6 months vs. 18 months, respectively, P = .84). According to microenvironmental evaluations, lower stromal score (defined as stroma having less desmoplasia and rich in cells) and presence of peritumoral Crohn’s-like inflammatory response were associated with higher survival (29.2 months vs. 19.7 months for low vs. high stromal scores, respectively, P = .16 and 30.2 months vs. 18.1 months for the presence of Crohn’s-like inflammatory response P = .13). Decreased survival was observed in tumors with increased CD204+ tumor-associated macrophages which were immunosuppressive elements of the microenvironment (12 months vs. 26.3 months for intra-tumoral assessment, P = .29). Conclusion: Tissue-resident memory T cells and other microenvironmental features may be prognostic in resectable pancreatic ductal adenocarcinomas. Further studies with larger cohorts are needed for validation.

Tissue-resident memory T cells in the era of (Neo) adjuvant melanoma management

“…This finding has critical therapeutic importance given the recent successful development of combination anti-LAG-3 with anti-PD-1 in metastatic melanoma ( 19 ). Moreover, tumor-infiltrating T RM correlate with longer disease-free periods and OS in patients of cSCC ( 20 , 21 ), breast ( 22 ), ovarian ( 23 ), endometrial ( 24 ), pancreatic ductal adenocarcinoma ( 25 ) and lung cancer ( 26 , 27 ) which further exemplifies the importance of this T cell subset in cancer outcomes.…”

The molecular mechanism of actions and clinical utilities of tumor infiltrating lymphocytes in gastrointestinal cancers: a comprehensive review and future prospects toward personalized medicine

“…Decreased survival was observed in tumors with increased CD204 + tumorassociated macrophages, which were immunosuppressive elements of the microenvironment (P-value = 0.29). Also, there was no correlation between the expression of PDL-1 + and survival in 81 operated PDAC tissues (87).…”

“…Samples from intra-tumoral and peritumoral areas for evaluating tissue-resident memory cells, TILs, CD204 + macrophages, tumor stroma, and PDL1 + have been collected and underwent the staining process. Higher expression of intra-tumoral tissue-resident memory cell counts was associated with better survival (P-value = 0.84) in PDAC patients (87). Decreased survival was observed in tumors with increased CD204 + tumorassociated macrophages, which were immunosuppressive elements of the microenvironment (P-value = 0.29).…”

“…The members of tissue-resident memory T-cells induce their anti-cancer effects through overexpression of E-cadherin and improve the cytotoxicity of Tcells (133). A study on 81 operated PDAC patients was done to investigate the prognostic role of tissue-resident memory T-cell and TME features (87). Samples from intra-tumoral and peritumoral areas for evaluating tissue-resident memory cells, TILs, CD204 + macrophages, tumor stroma, and PDL1 + have been collected and underwent the staining process.…”

Tissue-Resident Memory T Cells in Gastrointestinal Cancers: Prognostic Significance and Therapeutic Implications

“…With further study, it has become apparent that the abundance of Trm cells is a vital determinant of patient survival. In pancreatic cancer patients, those with a higher abundance of Trm cells tended to survive longer compared with those with lower numbers [ 47 ]. In left-sided CRC, the presence of activated Trm cells (not CD8 alone) was prognostically significant, and patients with low numbers of activated Trm cells exhibited a poor prognosis, even with high CD8 T-cell infiltration.…”