肿瘤免疫编辑理论与树突状细胞个体化治疗肿瘤策略的思考

利用树突状细胞瘤苗提高机体免疫系统对肿瘤的特异杀伤能力,已成为肿瘤免疫治疗中的研究热点.根据肿瘤免疫编辑理论,肿瘤免疫可分为清除、平衡和逃逸3个阶段.应用该理论阐述应用树突状细胞个体化治疗肿瘤的策略具有重要意义.     

肿瘤免疫编辑与免疫治疗

Schreiber等人于2002年提出肿瘤免疫编辑学说。肿瘤免疫编辑分为3个阶段:清除阶段、均衡阶段和逃逸阶段。肿瘤免疫编辑学说较全面的阐释了肿瘤与宿主免疫系统之间的复杂的相互作用。肿瘤免疫编辑学说对肿瘤免疫治疗具有一定的指导意义。依据肿瘤免疫治疗实践,提出了肿瘤免疫编辑和肿瘤免疫治疗的一些观点。     

肿瘤免疫编辑与免疫治疗

Schreiber等人于2002年提出肿瘤免疫编辑学说.肿瘤免疫编辑分为3个阶段:清除阶段、均衡阶段和逃逸阶段.肿瘤免疫编辑学说较全面的阐释了肿瘤与宿主免疫系统之间的复杂的相互作用.肿瘤免疫编辑学说对肿瘤免疫治疗具有一定的指导意义.依据肿瘤免疫治疗实践,提出了肿瘤免疫编辑和肿瘤免疫治疗的一些观点.     

肿瘤疫苗治疗肿瘤的前景

肿瘤疫苗的发展已经历了一个多世纪,20世纪50年代,人们开始了自体肿瘤疫苗的研究.使肿瘤疫苗(主动性免疫治疗)成为继手术、放疗、化疗之后的肿瘤治疗方法.肿瘤疫苗作为主动特异性免疫治疗,在临床中起到越来越重要的作用,人们开始尝试利用多种方法制备肿瘤疫苗并利用其促进机体免疫应答,从整体细胞,分子水平调控机体对肿瘤的免疫.目前肿瘤疫苗的研制已取得很大进展,给人类战胜肿瘤提供很大希望。     

从自然选择学说看肿瘤免疫

当今人类生存的环境发生了变化,肿瘤的发病率和病死率也越来越高,肿瘤细胞面对强大的免疫系统生存下来,说明肿瘤生存能力增强已经适应了其生存环境,这是环境对肿瘤细胞自然选择的结果。自然选择学说始终贯穿于肿瘤免疫学的免疫监视理论和免疫编辑学说之中,从自然选择的角度看肿瘤免疫学,将为肿瘤治疗策略开创一条新路。     

肿瘤抗原与肿瘤免疫

通过自身的免疫系统对肿瘤细胞进行杀灭已成为极具潜力的抗肿瘤手段。肿瘤抗原与机体对肿瘤细胞的免疫之间形成了一个此消彼长的矛盾关系,研究肿瘤研究自身的免疫学特性以及肿瘤细胞的免疫原性之间相互关系的问题已成为当前研究中的热点。一方面,可利用增强肿瘤细胞的抗原性来增强机体的免疫排斥反应;另一方面,纠正机体免疫系统的功能障碍,以增强其刺激免疫应答的能力,并辨证地分析了这两方面在肿瘤免疫排斥中的作用及相应的解决对策。     

肿瘤疫苗治疗肿瘤的前景

肿瘤疫苗的发展已经历了一个多世纪,20世纪50年代,人们开始了自体肿瘤疫苗的研究.使肿瘤疫苗(主动性免疫治疗)成为继手术、放疗、化疗之后的肿瘤治疗方法.肿瘤疫苗作为主动特异性免疫治疗,在临床中起到越来越重要的作用,人们开始尝试利用多种方法制备肿瘤疫苗并利用其促进机体免疫应答,从整体细胞,分子水平调控机体对肿瘤的免疫.目前肿瘤疫苗的研制已取得很大进展,给人类战胜肿瘤提供很大希望.     

肿瘤免疫治疗需要综合性

自从人们发现肿瘤与免疫有密切关系以来,对肿瘤免疫治疗寄予了厚望,然而,由于免疫机制、免疫途径的网络性和复杂性,免疫治疗未从根本上改变肿瘤治疗的现状,而仅仅是传统治疗手段的有益补充.     

临床肿瘤免疫的研究近况

免疫系统具有特异性破坏肿瘤而不损伤正常组织的能力,并且可以产生长久记忆从而阻止肿瘤复发。过去30年的肿瘤免疫研究充分证明肿瘤可以被免疫系统识别,并且机体免疫监视可以阻止肿瘤的发展或长期控制。目前的临床试验提示免疫治疗可能成为肿瘤治疗非常重要的一部分,试验中发现免疫相关的毒性、疗效评价标准以及观察终点与传统的细胞毒药物及靶向治疗均存在很大的差别。为了充分发挥免疫治疗的疗效,研究者需要更深入地了解肿瘤与宿主免疫反应之间动力学关系以及肿瘤的免疫逃逸机制,识别、评价及处理免疫相关反应。     

调节性T细胞与肿瘤免疫治疗

调节性T细胞在肿瘤免疫逃逸过程中起着举足轻重的作用.随着人们对肿瘤微环境的认识的加深及治疗思路的改变,调节性T细胞在肿瘤治疗方面的应用将会日趋成熟,为肿瘤的治疗提供了新的机遇,同时,如何平衡调节性T细胞正反两方面的作用,也将会对我们提出新的挑战.     

肿瘤免疫中的细胞凋亡

在肿瘤免疫编辑的三个阶段：清除、平衡和逃逸,细胞凋亡发挥重要作用。清除阶段,免疫细胞通过诱导肿瘤细胞凋亡发挥免疫清除作用;平衡阶段,在免疫选择作用下,肿瘤细胞凋亡促进肿瘤恶性演进;逃逸阶段,肿瘤细胞凋亡耐受性增强,进而反向促使免疫细胞凋亡,削弱肌体免疫力,产生免疫耐受。     

Cancer Worry,Perceived Risk and Cancer Screening in First-Degree Relatives of Patients with Familial Gastric Cancer

Currently, there is a lack of evidence evaluating the psychological impact of cancer-related risk perception and worry in individuals at high risk for gastric cancer. We examined the relationships between perceived risk, cancer worry and screening behaviors among first-degree relatives (FDRs) of patients with familial gastric cancer. FDRs of patients diagnosed with familial gastric cancer with a non-informative genetic analysis were identified and contacted. Participants completed a telephone interview that assessed socio-demographic information, cancer risk perception, cancer worry, impact of worry on daily functioning, and screening behaviors. Twenty-five FDRs completed the telephone interview. Participants reported high levels of comparative and absolute cancer risk perception, with an average perceived lifetime risk of 54 %. On the other hand, cancer-related worry scores were low, with a significant minority (12 %) experiencing high levels of worry. Study participants exhibited high levels of confidence (median = 70 %) in the effectiveness of screening at detecting a curable cancer. Participants that had undergone screening in the past showed significantly lower levels of cancer-related worry compared to those that had never undergone screening. In conclusion, individuals at high-risk for gastric cancer perceived a very high personal risk of cancer, but reported low levels of cancer worry. This paradoxical result may be attributed to participants’ high levels of confidence in the effectiveness of screening. These findings highlight the importance for clinicians to discuss realistic risk appraisals and expectations towards screening with unaffected members of families at risk for gastric cancer, in an effort to help mitigate anxiety and help with coping.     

Cancer Genetics Service Interest in Women with a Limited Family History of Breast Cancer

Women with a limited family history of breast cancer may be interested in cancer genetics information although their objective risk of breast cancer may not indicate routine referral to cancer genetics services. This study examined factors related to interest and use of cancer genetics services in a community sample of women with a limited family history of breast cancer (N = 187) who had no previous contact with cancer genetics services. Participants provided demographic information and ratings of perceived risk, cancer distress, attitudes, and intentions to initiate cancer genetics services. Participants were given information about a cancer genetics clinic that served women having concerns about their breast cancer risk. Women were contacted within 6 weeks and 8 months following their study appointment. Six weeks following their study appointment, 25% of women had initiated cancer genetics services. Eight months following their study appointment, 18% of women reported having completed a cancer genetics service appointment. Baseline intentions independently predicted both initiation at 6 weeks and appointment at 8 months. Cancer distress was positively associated with cancer genetics service initiation and appointment. Results suggest that some women with a limited family history of breast cancer are interested in seeking out cancer genetics information. Women with a limited family history of breast cancer may benefit from the availability of cancer genetics information provided through primary healthcare settings.     

Ethnocultural Influences in Cancer

Compelling evidence that ethnicity is associated with serious disparities in cancer morbidity and mortality has been documented in the medical and public health literature. In addition to the role that socioeconomic variables play in affecting cancer outcomes, health professionals are beginning to pay attention to the influence of ethnicity and culture. This paper examines the role that ethnocultural factors contribute to cancer, with particular attention to breast, cervical, prostate, and colorectal cancers. Young and Zane's adaptation of a process oriented model of how culture and ethnicity affect disease is proposed as a useful framework to understand the illness experience. It is suggested that attending to ethnocultural issues will assist health providers and researchers toward developing and implementing strategies to improve cancer outcomes among ethnic populations.     

Acute Cancer Cognitive Therapy

The utility of cognitive therapy (CT) for ambulatory cancer patients is clear but the acute cancer setting significantly shapes the therapeutic interaction, parameters, and delivery of CT. In this article, we describe how to apply CT to acute cancer settings, focusing on how this approach differs from traditionally taught, ambulatory CT. We highlight the importance of a tailored history and formulation, how the cognitive model is applied within an acute cancer context to promote coping and adaptation. Reframing must consider the "grain of truth" to many so-called distorted cognitions, such as "cancer means death." Fear of recurrence is an example of a common reframing challenge. Another is the "tyranny of positive thinking." Here there is avoidance of considering negative outcomes such as death; patients are told to "think positive," leaving them alone at a time of life-threatening crisis. Instead, acute cancer CT utilizes a stance of realistic optimism. Empathy plays a vital role in turning off the bracing reaction to threat and facilitating problem-solving. Successfully combining CT with medications is integral to this model. We also discuss how CT can be applied to discussing prognosis, the desire for hastened death and suicidality, as well as death and dying in general. Because of the ubiquitous nature of cancer, most cognitive therapists will encounter patients with cancer in their practices. Acute cancer CT is a skill set that should be widely taught to cognitive therapists and flagged as a priority for academic programs and professional organizations.     

Cancer Victim Identity for Individuals with Histories of Cancer and Childhood Sexual Abuse

Identifying as a ‘cancer victim’ has been linked to adverse psychosocial sequelae in individuals who have been diagnosed with cancer. Being a childhood sexual abuse (CSA) survivor may predispose individuals towards a “victim” identity in general. The aim of this study was to determine the prevalence of identifying as a ‘cancer victim’ among CSA survivors who were diagnosed with cancer as adults, and to explore psychological factors associated with identification as a cancer victim. 105 adults reporting both a history of CSA and of having been diagnosed with cancer as an adult were recruited through Amazon Mechanical Turk. Variables assessed included CSA severity, abuse-related powerlessness, general mastery, and cancer victim identity. Fifty-one percent of the sample endorsed a cancer victim identity. Path analysis revealed that abuse-related powerlessness was related to decreased feelings of general mastery, which was in turn associated with cancer victim identification (x ² = .12, DF = 1, p < .73; RMSEA = .00; SRMR = .01: Bentler CFI = 1.0). From a clinical perspective, the results suggest that increasing general mastery in CSA survivors in the cancer setting may be an important mechanism for attenuating the risk for developing a cancer victim identity and, presumably, for downstream adverse psychosocial sequelae.     

On Using a Cancer Center Cancer Registry to Identify Newly Affected Women Eligible for Hereditary Breast Cancer Syndrome Testing: Practical Considerations

The goals of this research were to describe the process of identifying and recruiting individuals registered with a cancer center's cancer registry who were eligible to participate in cancer genetic research. This study specifically focused on younger women with personal and family cancer histories strongly suggestive of hereditary breast cancer syndromes, as determined by genetic counselor review. Of special interest was to determine the proportion of women from minority backgrounds who were (a) identifiable in this manner and (b) interested in genetic testing for hereditary breast cancer through a family cancer clinical research program. An initial query of the 292 cases of women newly affected with breast cancer and contained within the registry indicated that 124 met demographic eligibility criteria. The personal and family cancer histories of each of these women were then reviewed by a genetic counselor and the remaining, eligible patients (n = 31) were subsequently contacted by mail and telephone: approximately three-fifths (18/31) of these patients were White and two-fifths (13/31) were Black or of another racial background. Of the women who were sent one or more study-related mailings, 10% (3/31) were unreachable by telephone due to incorrect contact information, 32% (10/31) were reachable by telephone but unresponsive to messages left, 26% (8/31) had already participated in the family cancer program (i.e., were positive controls), 6% (2/31) were interested in participating in the program, 23% (7/31) were uninterested in participating in the program, and 3% (1/31) were later determined to be ineligible. Comparing the racial backgrounds of women who were either positive controls or interested in participating (i.e., “tester” category) to women who were either unreachable, nonresponsive, uninterested, or ineligible (i.e., “nontester” category), there was a nonsignificant trend for more non-White women to fall into the nontester than tester category, Fisher's Exact Test = .09. This work underscores practical steps in planning and carrying-out cancer genetic testing research among women newly affected with breast cancer and members of special populations. It also underscores the role that genetic counseling professionals play in this process.