Research shows that forms of participation among youth are strongly differentiated and connected with complex meanings and motivations. A growing sector of youth develops political intervention ...through the adoption of distinctive everyday practices and lifestyles. The article aims to reflect upon dress among young activists involved in political groups. Very little research focuses on this topic, but following studies on everyday politics, the young activists’ clothing could be considered as a form and a field of political participation. This approach, however, seems not to be sufficient to interpret the phenomenon. Taking inspiration from research about youth cultures, the article suggests interpreting youth clothing conjointly as a component of style, as a means for constructing collective identity, and social positioning. The article is based on qualitative interviews collected in Piedmont (Italy). Six main topics have been investigated: 1. Socialization to clothing; 2. clothing of the activists and in their groups; 3. meanings of clothing; 4. relevance of clothing; 5. practices of buying clothes; 6. clothes as consumer goods.
Nowadays a lot of research describes most young people as barely interested in politics, expressing little trust in political institutions and far from any forms of institutional political ...participation. Moreover, most of the engaged youth are involved in forms of participation described as more civic and social than political, weakly ideological, more and more often digital and developed in virtual space, and usually experienced as one among several components of everyday personal lives. The article explores youth activism in political squats because it is a form of participation which, in countertendency, is political and radical in its aims and strategies, explicitly ideologically inspired, strongly rooted in physical places, and often quite central in everyday personal lives. The text is based on research conducted in the city of Turin (Italy) by means of qualitative interviews, participant observation and document analysis. Four main interconnected thematic dimensions are considered: Individuals’ biographical paths and meanings of activism; distinctive lifestyles and cultural sensitivities among the activists; collective narratives about contemporary society and possibilities of social change; patterns of intervention and forms of organization. On the basis of these analyses, the article maintains that this form of activism can be usefully interpreted as a real lifestyle, which has an explicit and intense political sense, but which young activists also connect with a much wider, more differentiated set of meanings.
In the last decade, the treatment of non-small cell lung cancer (NSCLC) has been revolutionized by the introduction of immune checkpoint inhibitors (ICI) directed against programmed death protein 1 ...(PD-1) and its ligand (PD-L1), or cytotoxic T lymphocyte antigen 4 (CTLA-4). In spite of these improvements, some patients do not achieve any benefit from ICI, and inevitably develop resistance to therapy over time. Tumor microenvironment (TME) might influence response to immunotherapy due to its prominent role in the multiple interactions between neoplastic cells and the immune system. Studies investigating lung cancer from the perspective of TME pointed out a complex scenario where tumor angiogenesis, soluble factors, immune suppressive/regulatory elements and cells composing TME itself participate to tumor growth. In this review, we point out the current state of knowledge involving the relationship between tumor cells and the components of TME in NSCLC as well as their interactions with immunotherapy providing an update on novel predictors of benefit from currently employed ICI or new therapeutic targets of investigational agents. In first place, increasing evidence suggests that TME might represent a promising biomarker of sensitivity to ICI, based on the presence of immune-modulating cells, such as Treg, myeloid derived suppressor cells, and tumor associated macrophages, which are known to induce an immunosuppressive environment, poorly responsive to ICI. Consequently, multiple clinical studies have been designed to influence TME towards a pro-immunogenic state and subsequently improve the activity of ICI. Currently, the mostly employed approach relies on the association of "classic" ICI targeting PD-1/PD-L1 and novel agents directed on molecules, such as LAG-3 and TIM-3. To date, some trials have already shown promising results, while a multitude of prospective studies are ongoing, and their results might significantly influence the future approach to cancer immunotherapy.
The identification of inhibitory NK cell receptors specific for HLA-I molecules (KIRs and NKG2A) provided the molecular basis for clarifying the mechanism by which NK cells kill transformed cells ...while sparing normal cells. The direct interactions between inhibitory NK cell receptors and their HLA-I ligands enable NK cells to distinguish healthy from transformed cells, which frequently show an altered expression of HLA-I molecules. Indeed, NK cells can kill cancer cells that have lost, or under express, HLA-I molecules, but not cells maintaining their expression. In this last case, it is possible to use anti-KIR or anti-NKG2A monoclonal antibodies to block the inhibitory signals generated by these receptors and to restore the anti-tumor NK cell activity. These treatments fall within the context of the new immunotherapeutic strategies known as "immune checkpoint blockade." These antibodies are currently used in clinical trials in the treatment of both hematological and solid tumors. However, a more complex scenario has recently emerged. For example, NK cells can also express additional immune checkpoints, including PD-1, that was originally described on T lymphocytes, and whose ligands (PD-Ls) are usually overexpressed on tumor cells. Thus, it appears that the activation of NK cells and their potentially harmful effector functions are under the control of different immune checkpoints and their simultaneous expression could provide additional levels of suppression to anti-tumor NK cell responses. This review is focused on PD-1 immune checkpoint in NK cells, its potential role in immunosuppression, and the therapeutic strategies to recover NK cell cytotoxicity and anti-tumor effect.
Background
Rare cases of severe myocarditis are reported during treatment with nivolumab. Troponin, a biomarker of cardiac damage, is a key component of the diagnostic workup of many cardiac ...disorders, including myocarditis. This study investigates the role of troponin to assess cardiac involvement during nivolumab therapy for non‐small cell lung cancer (NSCLC).
Materials and Methods
We evaluated 59 NSCLC patients, analyzing serum samples collected within a translational research study. Troponin above the upper normal limit (0.046 ng/mL) was defined as Tn+, whereas normal but detectable troponin (0.015–0.045) was defined as Tndet. Troponin alterations were interpreted on the grounds of the following elements: peak values and time curve, cardiac comorbidities, signs and symptoms coincident to troponin elevation, ECG, echocardiography, and disease progression.
Results
No patient had cardiovascular events. Among 362 available blood samples, Tn+ (max 0.317 ng/mL) was found in 13 determinations belonging to 6 patients. Seven other patients had isolated Tndet. In five patients, Tn+ was attributed to cardiac comorbidities, disease progression, or worsening clinical status. One patient without cardiac history and in good clinical condition had a sustained troponin increase—soon after the start of therapy—and after careful evaluation of all relevant elements, it was interpreted as a marker of nivolumab‐related subclinical myocarditis.
Conclusion
Tn+ may occur in NSCLC patients treated with nivolumab, but in most cases it does not indicate nivolumab cardiotoxicity. In some cases, however, a careful interpretation of troponin alteration, especially at the beginning of therapy, enables identification of subclinical myocarditis, thus allowing early cardiac treatment.
Implications for Practice
Myocarditis is a rare but serious adverse event of immune checkpoint blockade with nivolumab, which needs to be recognized as soon as possible. This article suggests that troponin, a user‐friendly biomarker of myocardial cytotoxicity, might be useful for early detection of immune‐mediated myocarditis. However, because troponin abnormalities might also be related to a number of conditions capable of causing myocardial oxygen demand‐supply mismatch, a careful cardiac assessment should be performed in non‐small cell lung cancer patients in order to properly interpret any troponin increase. According to the available evidence, monitoring troponin during the first weeks of treatment can be considered reasonable.
摘要
背景. 在使用Nivolumab治疗期间报告了罕见的重症心肌炎病例。肌钙蛋白是心脏损伤的生物标志物,是诊断多种心脏疾病(包括心肌炎)的关键组成部分。本研究探讨肌钙蛋白在非小细胞肺癌(NSCLC)治疗中评估心脏受累程度所起的作用。
材料与方法.我们评估了59例NSCLC患者,分析了转化研究中采集的血清样本。高于正常上限的肌钙蛋白(0.046 ng/mL)定义为Tn+,而正常但可检测到的肌钙蛋白(0.015‐0.045)定义为 Tndet。肌钙蛋白的变化根据以下因素解释:峰值和时间曲线、心脏合并症、与肌钙蛋白升高相一致的症状和体征、ECG、超声心动图、疾病进展情况。
结果.患者未出现心血管事件。362份有效血样中,6例患者的13份血样测出Tn+(最高0.317 ng/mL)。另外7例患者仅检出Tndet。在5例患者中,Tn+被认为是心脏并发症、疾病进展或临床状况恶化所致。1例无心脏病史的患者,临床状况良好,治疗开始后不久肌钙蛋白持续升高,经仔细评估所有相关因素后,持续升高的肌钙蛋白解释为与Nivolumab相关的亚临床心肌炎的标志物。
结论.NSCLC患者使用Nivolumab治疗时可能出现Tn+,但在大多数情况下,并不代表Nivolumab有心脏毒性。然而,在某些情况下,仔细解释肌钙蛋白的变化,特别是在治疗开始时,可以识别亚临床心肌炎,从而使早期心脏治疗成为可能。
实践启示:心肌炎是一种罕见,但严重的免疫检查点阻断剂Nivolumab治疗的不良事件,需要尽快识别。本文认为肌钙蛋白是一种识别心肌细胞毒性有用的生物标志物,可用于早期发现免疫介导的心肌炎。然而,由于肌钙蛋白异常也可能与一些可能导致心肌氧供需不匹配的情况有关,因此应在非小细胞肺癌患者中仔细评估,正确解释任何肌钙蛋白增加的情况。根据现有证据,在治疗头几周监测肌钙蛋白被认为是合理的。
This article explores the potential role of seriated troponin assessments during treatment with nivolumab for advanced non‐small cell lung cancer as a biomarker of nivolumab‐related cardiac toxicity.
In the last years, natural killer (NK) cell-based immunotherapy has emerged as a promising therapeutic approach for solid tumors and hematological malignancies. NK cells are innate lymphocytes with ...an array of functional competences, including anti-cancer, anti-viral, and anti-graft-vs.-host disease potential. The intriguing idea of harnessing such potent innate immune system effectors for cancer treatment led to the development of clinical trials based on the adoptive therapy of NK cells or on the use of monoclonal antibodies targeting the main NK cell immune checkpoints. Indeed, checkpoint immunotherapy that targets inhibitory receptors of T cells, reversing their functional blocking, marked a breakthrough in anticancer therapy, opening new approaches for cancer immunotherapy and resulted in extensive research on immune checkpoints. However, the clinical efficacy of T cell-based immunotherapy presents a series of limitations, including the inability of T cells to recognize and kill HLA-I
tumor cells. For these reasons, new strategies for cancer immunotherapy are now focusing on NK cells. Blockade with NK cell checkpoint inhibitors that reverse their functional block may overcome the limitations of T cell-based immunotherapy, mainly against HLA-I
tumor targets. Here, we discuss recent anti-tumor approaches based on mAb-mediated blocking of immune checkpoints (either restricted to NK cells or shared with T cells), used either as a single agent or in combination with other compounds, that have demonstrated promising clinical responses in both solid tumors and hematological malignancies.
In the scenario of systemic treatment for advanced non-small cell lung cancer (NSCLC) patients, one of the most relevant breakthroughs is represented by targeted therapies. Throughout the last years, ...inhibitors of the epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), c-Ros oncogene 1 (ROS1), and V-raf murine sarcoma viral oncogene homolog B (BRAF) have been approved and are currently used in clinical practice. However, other promising molecular drivers are rapidly emerging as therapeutic targets. This review aims to cover the molecular alterations with a potential clinical impact in NSCLC, including amplifications or mutations of the mesenchymal-epithelial transition factor (MET), fusions of rearranged during transfection (RET), rearrangements of the neurotrophic tyrosine kinase (NTRK) genes, mutations of the Kirsten rat sarcoma viral oncogene (KRAS) and phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA), as well as amplifications or mutations of human epidermal growth factor receptor 2 (HER2). Additionally, we summarized the current status of targeted agents under investigation for such alterations. This revision of the current literature on emerging molecular targets is needed as the evolving knowledge on novel actionable oncogenic drivers and targeted agents is expected to increase the proportion of patients who will benefit from tailored therapeutic approaches.
Small cell lung cancer (SCLC) has been historically considered a homogeneous disease and thus approached as a single entity when it comes to clinical studies design and new treatments developments. ...However, increasing knowledge in the genetic and molecular landscape of this disease challenges this concept, opening the possibility that different subtypes might show differential vulnerability to treatments. In this narrative review, we gather the most relevant advances in genetic and molecular characterization of SCLC, focusing on how these discoveries may be used to design the path for a personalized treatment approach. Indeed, we discuss the new classification based on differential protein expression, the prevalence and significance of oncogenic drivers (e.g.,
mutations and
rearrangements) in SCLC, the genetic characteristics of SCLC in patients with no smoking history, and the existing evidence supporting the use of liquid biopsy for capturing the heterogeneity of the disease. We use the keywords "small cell lung cancer", "SCLC", "EGFR", "ALK", "histological transformation", and "transcriptional factors" to identify original research manuscripts, clinical trials, case reports, and case series from PubMed.
Immune checkpoint blockade represents a major breakthrough in advanced non-small cell lung cancer (NSCLC) therapy. However, success is limited to a subset of patients and there is a critical need to ...identify robust biomarkers associated with clinical response. In this study, we assessed whether pre-existing immunological characteristics, as well as immune parameters measured during treatment, might provide such clinical guidance. We studied blood samples collected at baseline and during treatment in a cohort of advanced NSCLC patients (
= 74) treated with nivolumab. Several lymphocyte subsets and biomarkers were then correlated with overall survival (OS) as well as clinical response, assessed using RECIST criteria. We found that patients characterized by longer OS had higher levels of CD3
, CD4
, and CD8
T cells but lower levels of NK cells at baseline. Moreover, that they displayed a statistically significant lower expression of PD-1 on both CD3
and CD8
T cells (
= 0.013 and
= 0.033, respectively). The pre-treatment level of exhausted T cells (CD8
PD1
Eomes
) was significantly lower in patients with controlled disease (CD), defined as partial response (PR), and stable disease (SD), compared to those with progressive disease (PD) (
= 0.046). In CD patients, the frequency of exhausted CD8
T cells further decreased during treatment cycles (
= <0.0001,
= 0.0032, and
= 0.0239, respectively). In conclusion, our results suggest that the distribution of lymphocyte subsets and expression of PD-1 on T cells before treatment may help predict the outcome of anti-PD-1 treatment in NSCLC patients. In addition, assessing the initial levels of exhausted T cells as well as their decrease upon treatment may also predict response and clinical outcome.
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