Immunotherapy in Pancreatic Cancer: Why Do We Keep Failing? A Focus on Tumor Immune Microenvironment, Predictive Biomarkers and Treatment Outcomes.
Immunotherapy in Pancreatic Cancer: Why Do We Keep Failing? A Focus on Tumor Immune Microenvironment, Predictive Biomarkers and Treatment Outcomes.
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胰腺癌的免疫治疗：为什么我们一直失败？关注肿瘤免疫微环境、预测性生物标志物和治疗结果。
作者：
在胰腺癌中，免疫疗法和靶向疗法并没有带来在其他恶性肿瘤中观察到的治疗革命。解释这种差异的原因之一是胰腺肿瘤微环境可能起着至关重要的作用，它具有独特的特征，不同于其他肿瘤。本综述的目的是提供胰腺癌独特的肿瘤免疫微环境的全面概述，并总结有关在这种癌症中使用免疫治疗和免疫生物标志物的现有数据。免疫疗法和靶向疗法的出现极大地改变了许多恶性肿瘤患者的预后。胰腺癌（PC）仍然是少数几种不用新一代疗法治疗的肿瘤之一，因为化疗仍然是晚期疾病的唯一有效治疗策略。旨在重新激活宿主免疫系统对抗癌细胞的药物，如靶向免疫检查点的药物，未能表现出显著的活性，尽管这些治疗在其他肿瘤中取得了成功。在许多情况下，在早期试验中获益的患者比例太小，无法预测，无法证明大型研究的合理性。具有高微卫星不稳定性/错配修复缺陷的PC患者人群是目前唯一可能受益于免疫治疗的人群;然而，这些改变的患病率太低，无法确定该肿瘤治疗方案的真实的变化。免疫治疗不成功的原因可能在于极其特殊的肿瘤微环境，包括独特的免疫组成和不同细胞之间的串扰。这些独特的特征也可以解释为什么通常用于预测其他肿瘤免疫治疗疗效的生物标志物在PC中似乎是无用的。在本文中，我们对PC中的免疫治疗进行了全面和最新的综述，从肿瘤免疫微环境的分析到免疫生物标志物和治疗结果，旨在强调简单地转移在其他肿瘤中获得的免疫治疗知识可能不是受PC影响的患者的成功策略。
In pancreatic cancer, immunotherapy and targeted therapies have not brought about the therapeutic revolution that has been observed in other malignancies. Among the reasons to explain this difference is the possibly crucial role played by the pancreatic tumor microenvironment, which has unique features and is different from that of other neoplasms. The aim of this review is to provide a comprehensive overview of the distinctive tumor immune microenvironment of pancreatic cancer and to summarize existing data about the use of immunotherapy and immune biomarkers in this cancer. The advent of immunotherapy and targeted therapies has dramatically changed the outcomes of patients affected by many malignancies. Pancreatic cancer (PC) remains one the few tumors that is not treated with new generation therapies, as chemotherapy still represents the only effective therapeutic strategy in advanced-stage disease. Agents aiming to reactivate the host immune system against cancer cells, such as those targeting immune checkpoints, failed to demonstrate significant activity, despite the success of these treatments in other tumors. In many cases, the proportion of patients who derived benefits in early-phase trials was too small and unpredictable to justify larger studies. The population of PC patients with high microsatellite instability/mismatch repair deficiency is currently the only population that may benefit from immunotherapy; nevertheless, the prevalence of these alterations is too low to determine a real change in the treatment scenario of this tumor. The reasons for the unsuccess of immunotherapy may lie in the extremely peculiar tumor microenvironment, including distinctive immune composition and cross talk between different cells. These unique features may also explain why the biomarkers commonly used to predict immunotherapy efficacy in other tumors seem to be useless in PC. In the current paper, we provide a comprehensive and up-to-date review of immunotherapy in PC, from the analysis of the tumor immune microenvironment to immune biomarkers and treatment outcomes, with the aim to highlight that simply transferring the knowledge acquired on immunotherapy in other tumors might not be a successful strategy in patients affected by PC.
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DOI：
10.3390/ph14070677
发表时间：
2021-07-15
期刊：
Pharmaceuticals (Basel, Switzerland)
影响因子：
--
作者：
Di Federico A;Tateo V;Parisi C;Formica F;Carloni R;Frega G;Rizzo A;Ricci D;Di Marco M;Palloni A;Brandi G
通讯作者：
Brandi G
DOI：
10.1126/science.aac9935
发表时间：
2016-04-08
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Casey SC;Tong L;Li Y;Do R;Walz S;Fitzgerald KN;Gouw AM;Baylot V;Gütgemann I;Eilers M;Felsher DW
通讯作者：
Felsher DW
影响因子：
50.3
作者：
Bear AS;Vonderheide RH;O'Hara MH
通讯作者：
O'Hara MH
影响因子：
4.4
作者：
Carrega, Paolo;Bonaccorsi, Irene;Ferlazzo, Guido
通讯作者：
Ferlazzo, Guido
影响因子：
11.2
作者：
De Monte, Lucia;Wormann, Sonja;Protti, Maria Pia
通讯作者：
Protti, Maria Pia