Precursor Lesions of Pancreatic Cancer

Kim, Joo Y; Hong, Seung‐Mo

doi:10.1159/000493554

Cited by 45 publications

(35 citation statements)

References 87 publications

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“…With our findings above at hand, it would be highly relevant to test immune responses in patients with RAS -mutant cancers and clarify if these patients display an attenuated immune response to the mutant epitopes, which would add impetus to the notion of the evolution of RAS -mutant cancer due to tumor immune evasion. The translational relevance of our findings would be to identify patients with premalignant RAS -mutant lesions, such as patients with precursor pancreatic cancer lesions [ 41 ], and perform vaccinations with RAS -mutant-derived epitopes to enhance the RAS -mutant-specific immune response, in order to facilitate clearing of the pre-malignant lesion.…”

Section: Discussionmentioning

confidence: 99%

Healthy Donors Harbor Memory T Cell Responses to RAS Neo-Antigens

Holmström

Andersen

2020

Cancers

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The RAS mutations are the most frequently occurring somatic mutations in humans, and several studies have established that T cells from patients with RAS-mutant cancer recognize and kill RAS-mutant cells. Enhancing the T cell response via therapeutic cancer vaccination against mutant RAS results in a clinical benefit to patients; thus, T cells specific to RAS mutations are effective at battling cancer. As the theory of cancer immuno-editing indicates that healthy donors may clear malignantly transformed cells via immune-mediated killing, and since T cells have been shown to recognize RAS-mutant cancer cells, we investigated whether healthy donors harbor T-cell responses specific to mutant RAS. We identified strong and frequent responses against several epitopes derived from the RAS codon 12 and codon 13 mutations. Some healthy donors demonstrated a response to several mutant epitopes, and some, but not all, exhibited cross-reactivity to the wild-type RAS epitope. In addition, several T cell responses were identified against mutant RAS epitopes in healthy donors directly ex vivo. Clones against mutant RAS epitopes were established from healthy donors, and several of these clones did not cross-react with the wild-type epitope. Finally, CD45RO+ memory T cells from healthy donors demonstrated a strong response to several mutant RAS epitopes. Taken together, these data suggest that the immune system in healthy donors spontaneously clears malignantly transformed RAS-mutant cells, and the immune system consequently generates T-cell memory against the mutations.

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Section: Discussionmentioning

confidence: 99%

Healthy Donors Harbor Memory T Cell Responses to RAS Neo-Antigens

Holmström

Andersen

2020

Cancers

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“…Transformation of normal pancreatic epithelium into malignant cells seems to cross in many cases through premalignant lesions, namely the pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasm (IPMN) (32). In support of this hypothesis, genomic analysis of PanIN and IPMN showed that they share the same genetic alterations of PDAC, although with lower incidence (33).…”

Section: Pdac Evolution: From Pancreatic Gland To Metastasismentioning

confidence: 94%

Adjuvant Treatment in Pancreatic Cancer: Shaping the Future of the Curative Setting

et al. 2021

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Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease even in the early stages, despite progresses in surgical and pharmacological treatment in recent years. High potential for metastases is the main cause of therapeutic failure in localized disease, highlighting the current limited knowledge of underlying pathological processes. However, nowadays research is focusing on the search for personalized approaches also in the adjuvant setting for PDAC, by implementing the use of biomarkers and investigating new therapeutic targets. In this context, the aim of this narrative review is to summarize the current treatment scenario and new potential therapeutic approaches in early stage PDAC, from both a preclinical and clinical point of view. Additionally, the review examines the role of target therapies in localized PDAC and the influence of neoadjuvant treatments on survival outcomes.

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“…Von pathohistologischer Seite werden dabei beschrieben bzw. neu definiert: pankreatische intraepitheliale Neoplasie (PanIns), intraduktal papillär muzinöse Neoplasie (IPMN), intraduktal tubulopapilläre Neoplasie (ITPN), intraduktal onkozytisch papilläre Neoplasie (IOPN), muzinös zystische Neoplasie (MCN) [22,23].…”

Section: Precursor Lesionsunclassified

Frühdiagnose des Pankreaskarzinoms – Die Rolle von Endosonografie und Sonografie

Schorr¹,

Essig²

2021

Z Gastroenterol

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ZusammenfassungPankreaskarzinome sind im Vergleich zu anderen Tumorarten relativ selten, die Prognose ist aber weiterhin schlecht, da die Tumoren meist in einem fortgeschrittenen Stadium diagnostiziert werden. Eine Frühdiagnostik wäre für das Überleben sinnvoll, ein generelles Screening ist für die Allgemeinbevölkerung aufgrund der niedrigen Prävalenz nicht möglich. Ein Screening ist nur für spezielle Risikogruppen mit einem hohen/erhöhten Karzinomrisiko (Keimbahnmutationen, familiäres Pankreaskarzinom, muzinöse zystische Pankreastumoren) etabliert. Weitere Risikokonstellationen (Pankreatitis, Diabetes mellitus, Zigaretten- und Alkoholabusus) sollten jedoch beachtet werden, um frühe Neoplasien nicht zu übersehen. Bedeutung kommt insbesondere der transabdominellen Ultraschalluntersuchung als weit verbreitetem erstem Untersuchungsverfahren zu. Damit können bereits erste Verdachtsmomente mit hoher Sensitivität beschrieben und der Tumorverdacht kann durch Einsatz von Ultraschallkontrastmittel erhärtet werden. Die Endosonografie hat in der weiteren Diagnostik eine herausragende Bedeutung. Durch zusätzliche Verfahren mit Einsatz von Ultraschallkontrastmittel, Elastografie und Feinnadelpunktion ist in der Regel eine definitive Klärung mit hoher Sensitivität und Spezifität möglich mit dem Ziel, die bislang schlechte Prognose des Pankreaskarzinoms weiter zu verbessern.

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Precursor Lesions of Pancreatic Cancer

Cited by 45 publications

References 87 publications

Healthy Donors Harbor Memory T Cell Responses to RAS Neo-Antigens

Healthy Donors Harbor Memory T Cell Responses to RAS Neo-Antigens

Adjuvant Treatment in Pancreatic Cancer: Shaping the Future of the Curative Setting

Frühdiagnose des Pankreaskarzinoms – Die Rolle von Endosonografie und Sonografie

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