Integrated analysis of tertiary lymphoid structures in relation to tumor-infiltrating lymphocytes and patient survival in pancreatic ductal adenocarcinoma

Abstract

CD8 + TILs (multivariable OR, 11.0; 95% CI, 4.57-29.7, P < 0.0001) and CD45RO + TILs (multivariable OR, 2.65; 95% CI, 1.25-5.80, P = 0.01), but not with levels of FOXP3 + TILs. TLS was associated with longer pancreatic cancer-specific survival (multivariable hazard ratio, 0.37; 95% CI, 0.25-0.56, P < 0.0001) and favorable outcomes of adjuvant S-1treatment. TLS was not associated with driver gene alterations but tumor CD274 negative expression. ConclusionsOur comprehensive data supports the surrogacy of TLS for vigorous anti-tumor immune response characterized by high levels of helper and cytotoxic T cells and their prognostic role.

Tertiary lymphoid structures in tongue cancer: Association with clinicopathological parameters, preoperative S‐1 chemotherapy response, and prognosis

“…To date, only one paper has reported an association between TLSs and preoperative S-1 chemotherapy, which examined it in pancreatic cancer. 27 That study found a favorable outcome of the use of adjuvant S-1 treatment in patients with TLSs with pancreatic carcinoma. The immune system plays an important role in the antitumor effects of conventional anticancer chemotherapy-based therapies; the cytotoxic effects of 5-FU are caused by the induction of apoptosis in cancer cells and are enhanced by IFN-γ.…”

“…to be relatively high in pancreatic carcinoma patients presenting with TLSs. 27 Furthermore, there are findings of a concurrent increase in the number of Treg cells and MDSCs, which act as immunosuppressors around TLSs or locally in the tumor, suggesting that the presence of these Treg cells and MDSCs may adversely affect the ability of TLSs to produce effector and memory lymphocytes. 3,28 S-1 may enhance the antitumor effects of TLSs by decreasing these MDSCs.…”

“…Although TLSs alone were not predictive of prognosis, the presence of TLSs was suggested to be a factor indicating a favorable prognosis when considering the indication for preoperative S‐1 chemotherapy. To date, only one paper has reported an association between TLSs and preoperative S‐1 chemotherapy, which examined it in pancreatic cancer 27 . That study found a favorable outcome of the use of adjuvant S‐1 treatment in patients with TLSs with pancreatic carcinoma.…”

“…The immune system plays an important role in the antitumor effects of conventional anticancer chemotherapy‐based therapies; the cytotoxic effects of 5‐FU are caused by the induction of apoptosis in cancer cells and are enhanced by IFN‐γ. IFN‐γ plays a central role in the elimination of cancer cells, and its expression levels have been found to be relatively high in pancreatic carcinoma patients presenting with TLSs 27 . Furthermore, there are findings of a concurrent increase in the number of Treg cells and MDSCs, which act as immunosuppressors around TLSs or locally in the tumor, suggesting that the presence of these Treg cells and MDSCs may adversely affect the ability of TLSs to produce effector and memory lymphocytes 3,28 .…”

Comprehensive Genomic Analysis of the Prognostic and Immunological Characteristics of Tertiary Lymphoid structures and CD8+ T-cells in Pancreatic Ductal Adenocarcinoma

“…Also, the formation of TLSs is relevant to the CD8 + T-cell in ltration, TLSs with signi cant plasma cell in ltration is correlated with improved CD8 + T-cell in ltration and overall survival (OS) in ovarian cancer [14]. Recently, the positive correlation between tumor in ltrating CD8 + T-cell and TLSs in PDAC was proved by Takeshi Tanaka et al [15]. However, the relationship between the degree of TLSs together with CD8 + T-cell in ltration and the ICBs therapeutic responses in PDAC remains unclear.…”