Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal forms of cancer, characterized by a highly desmoplastic tumor microenvironment. One main risk factor is chronic pancreatitis (CP). Progression of CP to PDAC is greatly influenced by persistent inflammation promoting genomic instability, acinar–ductal metaplasia, and pancreatic intraepithelial neoplasia (PanIN) formation. Components of the extracellular matrix, including immune cells, can modulate this progression phase. This includes cells of the innate immune system, such as natural killer (NK) cells, macrophages, dendritic cells, mast cells, neutrophils, and myeloid-derived suppressor cells (MDSCs), either promoting or inhibiting tumor growth. On one hand, innate immune cells can trigger inflammatory responses that support tumor progression by releasing cytokines and growth factors, fostering tumor cell proliferation, invasion, and metastasis. On the other hand, they can also activate immune surveillance mechanisms, which can limit tumor development. For example, NK cells are cytotoxic innate lymphoid cells that are able to kill tumor cells, and active dendritic cells are crucial for a functioning anti-tumor immune response. In contrast, mast cells and MDSCs rather support a pro-tumorigenic tumor microenvironment that is additionally sustained by platelets. Once thought to play a role in hemostasis only, platelets are now recognized as key players in inflammation and cancer progression. By releasing cytokines, growth factors, and pro-angiogenic mediators, platelets help shape an immunosuppressive microenvironment that promotes fibrotic remodeling, tumor initiation, progression, metastasis, and immune evasion. Neutrophils and macrophages exist in different functional subtypes that can both act pro- and anti-tumorigenic. Understanding the complex interactions between innate immune cells, platelets, and early precursor lesions, as well as PDAC cells, is crucial for developing new therapeutic approaches that can harness the immune and potentially also the coagulation system to target and eliminate tumors, offering hope for improved patient outcomes.
胰腺导管腺癌（PDAC）是最具侵袭性和致命性的癌症之一，其特点是具有高度纤维增生的肿瘤微环境。慢性胰腺炎（CP）是其主要风险因素之一。CP向PDAC的进展受到持续性炎症的显著影响，这种炎症会促进基因组不稳定性、腺泡-导管化生以及胰腺上皮内瘤变（PanIN）的形成。细胞外基质的组成成分，包括免疫细胞，能够调控这一进展阶段。这涉及先天免疫系统的细胞，如自然杀伤（NK）细胞、巨噬细胞、树突状细胞、肥大细胞、中性粒细胞和髓源性抑制细胞（MDSCs），它们可能促进或抑制肿瘤生长。一方面，先天免疫细胞可通过释放细胞因子和生长因子引发炎症反应，从而支持肿瘤进展，促进肿瘤细胞增殖、侵袭和转移。另一方面，它们也能激活免疫监视机制，从而限制肿瘤发展。例如，NK细胞是具有细胞毒性的先天淋巴样细胞，能够杀伤肿瘤细胞；而活化的树突状细胞对于发挥抗肿瘤免疫反应至关重要。相比之下，肥大细胞和MDSCs更倾向于支持促肿瘤发生的肿瘤微环境，这种环境还受到血小板的维持。血小板曾被认为仅参与止血过程，如今已被认识到在炎症和癌症进展中扮演关键角色。通过释放细胞因子、生长因子和促血管生成介质，血小板有助于形成免疫抑制性微环境，从而促进纤维化重塑、肿瘤发生、进展、转移和免疫逃逸。中性粒细胞和巨噬细胞存在不同的功能亚型，既可发挥促肿瘤作用，也可发挥抗肿瘤作用。理解先天免疫细胞、血小板与早期前驱病变以及PDAC细胞之间复杂的相互作用，对于开发新的治疗方法至关重要。这些方法可以利用免疫系统以及潜在的凝血系统来靶向和消除肿瘤，为改善患者预后带来希望。
Innate Immunity and Platelets: Unveiling Their Role in Chronic Pancreatitis and Pancreatic Cancer
肿瘤(癌症)患者之家