Harnessing the immune system to improve cancer therapy

Papaioannou, Nikos E.; Beniata, Ourania V.; Vitsos, Panagiotis; Tsitsilonis, Ourania E.; Samara, Pinelopi

doi:10.21037/atm.2016.04.01

Cited by 259 publications

(176 citation statements)

References 103 publications

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“…Indeed, an immune-suppressive milieu is a common in the tumor microenvironment. Appropriate immune responses, which have been intensively studied in recent decades, play an important role in controlling cancer growth 51,52 . Lymphocytes are key mediators of immune surveillance and immune editing, and lymphocyte infiltration into the tumor microenvironment is a prerequisite for an immunologic antitumor reaction.…”

Section: Discussionmentioning

confidence: 99%

“…Lymphocytes are key mediators of immune surveillance and immune editing, and lymphocyte infiltration into the tumor microenvironment is a prerequisite for an immunologic antitumor reaction. High lymphocyte counts and infiltration of tumors by type I lymphocytes with greater dimensions are associated with a good prognosis in cancers such as colon, ovarian, lung, and breast cancer [51][52][53] . Figure 4.…”

Section: Discussionmentioning

confidence: 99%

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The platelet-to-lymphocyte ratio as a predictor of patient outcomes in ovarian cancer: a meta-analysis

Sun

et al. 2017

Climacteric

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Objectives: The platelet-to-lymphocyte ratio (PLR) is a predictive clinical biomarker for different cancers. However, the results of several studies investigating the association between the PLR and the prognosis of ovarian cancer have been inconclusive. Therefore, there is a need to conduct a metaanalysis to estimate the prognostic value of the PLR in ovarian cancer. Methods: We searched the EMBASE, Medline, PubMed, and Web of Science databases to identify clinical studies that had evaluated the association between the PLR and ovarian cancer prognosis. Outcomes evaluated included overall survival (OS) and progression-free survival (PFS). We also analyzed PLR differences between malignant ovarian masses and the controls. Results: Twelve relevant studies that comprised 2340 patients were selected for the meta-analysis. The results revealed that elevated PLR was significantly associated with poor OS (hazard ratio (HR) 1.63, 95% confidence interval (CI) 1.05-2.56, p < 0.01) and PFS (HR 1.61, 95% CI 1.03-2.51, p < 0.01). The PLRs in malignant cases were higher than in controls (mean difference ¼ 63.57, 95% CI 39.47-87.66, p < 0.00001). Conclusion: An elevated PLR is associated with poor prognosis in patients with ovarian cancer. The PLR could be employed as a prognostic marker in patients with ovarian cancer. ARTICLE HISTORY

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The platelet-to-lymphocyte ratio as a predictor of patient outcomes in ovarian cancer: a meta-analysis

Sun

et al. 2017

Climacteric

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“…Inhibiting the checkpoint system allows the immune system to recognize and kill cancer cells. 10 Inhibiting immune system checkpoint mechanisms may also prevent the elimination of harmful, autoreactive lymphocytes and lead to the diverse autoimmune complications observed. 11 Immune adverse events related to ICI are a relatively new and increasingly recognized phenomenon.…”

Section: Discussionmentioning

confidence: 99%

Clinical Reasoning: A 77-year-old man presenting with episodic expressive aphasia

et al. 2018

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A 77-year-old white man presented to the emergency department with a 1-week history of episodic expressive aphasia, lasting between 3 and 30 minutes and increasing in frequency. He denied any associated symptoms with the aphasia and between episodes returned to baseline. His medical history included psoriatic arthritis, remote biopsy-confirmed giant cell arteritis (GCA), and metastatic urothelial adenocarcinoma for which he was being treated with programmed death ligand 1 (PD-L1) checkpoint inhibitor therapy.Initial neurologic examination, including language evaluation, was normal. The patient's musculoskeletal examination revealed features of chronic arthritis with dorsal hand soft tissue atrophy and bony joint hypertrophy without active synovitis. There were no findings of cutaneous, cardiopulmonary, or gastrointestinal abnormalities.The patient's initial brain MRI (figure) showed acute infarction in the right internal capsule. MRI fluid-attenuated inversion recovery sequence was otherwise unremarkable with minimal evidence of small vessel disease. CT angiogram was striking for several focal areas of high-grade stenosis of the large intracranial vessels: the right internal carotid artery (ICA) terminus, the proximal left M1 segment, and the left A1 origin had near-complete stenosis. In contrast, the other intracranial and extracranial neck vessels were patent with minimal atherosclerotic disease.The patient was started on dual antiplatelet therapy (aspirin and Plavix) as well as high-dose statin for severe, symptomatic large vessel intracranial stenosis.Questions for consideration: 1. What are the potential causes of focal proximal stenosis of the large intracranial arteries? 2. Given this differential diagnosis, what additional workup is recommended? GO TO SECTION 2

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“…Currently, researchers are now looking for ways to modulate this therapy so it can be applied to more tumors, including tumors in the CNS [141]. Importantly, the effectiveness of strategies such as vaccine and immune checkpoint therapies rely on a strong response and presence of tumor infiltrating immune cells for antigen presentation, which is low in most brain tumors due to the limited presence of resident immune cells within the brain [141,181]. Some strategies to stimulate the immune response, such as adjuvants or tetanus and diphtheria boosters with vaccine administration have increased effectiveness [141,182,183].…”

Section: Cns Tumor Immunotherapies and Astrocytesmentioning

confidence: 99%

The Role of Astrocytes in Tumor Growth and Progression

Gronseth¹,

Wang²,

Harder³

et al. 2018

Astrocyte - Physiology and Pathology

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Current research is continually implicating the importance of astrocytes as active participants in neurological injury, disease, and tumor progression. This chapter will discuss some of these emerging concepts, especially as they relate to tumor biology. Astrocytes themselves can become tumorigenic, such as the case in gliomas, which often have aberrant signaling in key regulating genes of astrocyte development. Astrocytes secrete factors that maintain the tight junctions of the blood brain barrier (BBB), which in turn regulates the success or failure of metastatic cells extravasating into the brain. This astrocytic association with the brain vasculature also promotes brain tumor stem cell characteristics, which are known to be necessary for tumor initiation. Tumor cells within the brain make direct contacts with astrocytes through gap junctions, which subsequently lead to increased chemoresistance of the tumor cells. Astrocytes have also been shown to effect tumors cells via secretion of degradative enzymes, cytokines, chemokines, and growth factors, all of which have been shown to promote tumor cell proliferation, survival, and invasion. Thus, research in astrocyte biology and the role of astrocytes in the tumor microenvironment has and will likely continue to reveal novel targets for cancer intervention.

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Harnessing the immune system to improve cancer therapy

Cited by 259 publications

References 103 publications

The platelet-to-lymphocyte ratio as a predictor of patient outcomes in ovarian cancer: a meta-analysis

The platelet-to-lymphocyte ratio as a predictor of patient outcomes in ovarian cancer: a meta-analysis

Clinical Reasoning: A 77-year-old man presenting with episodic expressive aphasia

The Role of Astrocytes in Tumor Growth and Progression

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