Peripheral ENO1-specific T cells mirror the intratumoral immune response and their presence is a potential prognostic factor for pancreatic adenocarcinoma

Abstract

Abstract. Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with an average survival of 4-6 months following diagnosis. Surgical resection is the only treatment with curative intent, but resectable PDAC patients are in the minority. Also, unlike other neoplasms, PDAC is resistant to conventional and targeted chemotherapy. Innovative treatments, such as immunotherapy, can be very important and the study of the immune response is fundamental. We previously demonstrated that PDAC patients show tumor-infiltrating T cells specific to α-enolase (ENO1), a glycolytic enzyme overexpressed by pancreatic tumor cells, which plays an important role in promoting cell migration and cancer metastasis. In the present study, we evaluate the functional anticancer proprieties of ENO1-specific T cells isolated from the peripheral blood of PDAC patients. Furthermore, comparing the T cell receptor repertoire of ENO1-specific peripheral and infiltrating tumor T cells from the same patient suggests that ENO1-specific T cells, despite having a different functional profile, can recirculate from the tumor to the periphery. Finally, of clinical relevance, the presence of peripheral ENO1-specific T cells has a prognostic value and significantly correlates with a longer survival.

Depletion of tumor-associated macrophages switches the epigenetic profile of pancreatic cancer infiltrating T cells and restores their anti-tumor phenotype

“…15 Of note, peripheral ENO1-specific T cells mirror the intra-tumoral immune response and represent a promising candidate as a prognostic marker of survival. 17 Here, we analyzed PDA-infiltrating T cells to define their functional state and how they were reflected in their epigenetic landscape. Although some studies have addressed the question of the number of PDA-infiltrating T cells, 12 to our knowledge this is the first study that characterizes the epigenetic states of PDA-TILs.…”

“…[13][14][15][16] More recently, we have described that circulating ENO1-specific T cells can represent a prognostic marker due to their correlation with prolonged survival. 17 The status of T cells in cancer should be considered in the context of other immune cells, such as Tumor-Associated Macrophages (TAMs) or Myeloid-Derived Suppressor Cells (MDSCs). 18 Both these populations are known to create an immune suppressive environment through either the secretion of cytokines such as IL10 and TGFb, or the expression of inhibitory molecules such as CONTACT Paola Cappello, PhD, paola.cappello@unito.it; Francesco Novelli franco.novelli@unito.it CeRMS-Lab of Tumor Immunology, via Santena 5-10126, Torino.…”

Unlikely role of glycolytic enzyme ��-enolase in cancer metastasis and its potential as a prognostic biomarker

“…Autoantibodies generated against a-enolase in its capacity as a tumour-associated antigen represent an additional type of prognostic biomarker that may be assayed in serum. The presence of autoantibodies against a-enolase correlated with longer disease-free survival and overall survival in pancreatic and lung cancer patients [45,[85][86][87] [ Table 4]. Furthermore, compared with healthy individuals, a-enolase antibodies…”

“…Patients with > 20% peripheral a-enolase-specific T cells or anti-a-enolase antibodies showed a better OS [87] ccRCC Primary ccRCC tissue (n = 360) and TCGA dataset (n = 428)…”

DEK protein overexpression predicts poor prognosis in pancreatic ductal adenocarcinoma

“…Despite continuous progress in diagnosis and treatment in recent decades, PDAC remains a great clinical challenge due to its dismal prognosis (2)(3)(4)(5)(6)(7). Currently, the key obstacle to progress is the lack of accurate and specific targets for the early diagnosis of PDAC (8)(9)(10). Therefore, the identification of novel biomarkers and development of new therapeutic approaches are of great value for PDAC.…”