Lymphatic Vessels, Inflammation, and Immunity in Skin Cancer

Lund, Amanda W.; Medler, Terry R.; Leachman, Sancy A.; Coussens, Lisa M.

doi:10.1158/2159-8290.cd-15-0023

Cited by 77 publications

(73 citation statements)

References 151 publications

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“…We have previously reported that blood and lymphatic vessel density is increased in the scalp compared to torso and extremity, as indicated by CD31 and D2-40 staining, respectively [20]. Although correlations between lymphatic density and melanoma metastasis has been reported [21], the issue remains controversial [22] and a histological study of scalp melanomas found high rates of both vascular and lymphatic invasion [23]. In addition, Hung et al[24] observed angiotropism in 14/20 primary tumors that developed BM.…”

Section: Discussionmentioning

confidence: 99%

Risk factors for development of melanoma brain metastasis and disease progression: a single-center retrospective analysis

Gardner¹,

Ward

Andtbacka

et al. 2017

Melanoma Research

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Objective Melanoma metastasis to the brain is associated with poor prognosis. We sought to determine patient demographics and primary tumor factors associated with development of brain metastasis (BM) and survival. We also investigated whether the BM detection setting (routine screening vs. symptomatic presentation) affected clinical outcomes. Methods A database of melanoma patients seen from 1999-2015 at our institution was reviewed to identify patients that developed BM. Patients with BM were matched by initial stage with patients who did not develop BM as a control group. Patient demographics, primary tumor characteristics, and clinical outcomes were analyzed. Results 123 patients with BM were matched by initial presenting stage to 237 patients without BM. Characteristics of the primary melanoma tumor associated with BM development included location on the scalp (P=0.030), nodular histologic type (P=0.020) and Breslow depth >4mm (P=0.048), while location on the leg was associated with decreased BM risk (P=0.006). In patients with BM, time to first recurrence for melanomas of the scalp was significantly shorter (10.8 vs. 24.8 months, p=0.007) than non-scalp head and neck tumors. Patient stage, tumor depth, nodular type, and ulceration were also associated with worse clinical outcomes. There were no differences in clinical outcomes between patients whose BM were detected upon routine screening vs. upon symptomatic presentation. Conclusions Factors predictive of developing BM included primary scalp location, nodular type, and depth. In BM patients, scalp location, stage, tumor depth, nodular type and ulceration, but not detection setting, were associated with worse clinical outcomes.

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Section: Discussionmentioning

confidence: 99%

Risk factors for development of melanoma brain metastasis and disease progression: a single-center retrospective analysis

Gardner¹,

Ward

Andtbacka

et al. 2017

Melanoma Research

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“…It is estimated that as many as 20% of cancers are instigated by chronic inflammation or persistent infections (115). Inflammatory cytokines and cells are implicated in tumorigenesis and tumor progression in most sites, and have been extensively documented in cancers of the stomach (116, 118), colon (16, 35, 63), skin (3, 65, 78, 126, 128), liver (4, 8, 41), breast (2, 21, 48), lung (32, 83, 100), and head/neck (12, 14, 15). …”

Section: The Role Of Inflammation In Cancer Initiationmentioning

confidence: 99%

Cancer and inflammation

Munn

2016

WIREs Mechanisms of Disease

198

134

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The relationship between inflammation and cancer has been recognized since the 17th century (6), and we now know much about the cells, cytokines and physiological processes that are central to both inflammation and cancer (39, 62, 66–68, 86, 92, 125). Chronic inflammation can induce certain cancers (11, 14, 27, 59, 61, 76, 79, 82), and solid tumors, in turn, can initiate and perpetuate local inflammatory processes that foster tumor growth and dissemination (7, 17, 67, 96). Consequently, inflammatory pathways have been targeted in attempts to control cancer (22, 46, 47). Inflammation is a central aspect of the innate immune system’s response to tissue damage or infection, and also facilitates the recruitment of circulating cells and antibodies of the adaptive immune response to the tissue. Components of the innate immune response carry out a robust, but sometimes overly-conservative response, sacrificing specificity for the sake of preservation. Thus, when innate immunity goes awry, it can have profound implications. How the innate and adaptive immune systems cooperate to neutralize pathogens and repair damaged tissues is still an area of intense investigation. Further, how these systems can respond to cancer, which arises from normal “self” cells that undergo an oncogenic transformation, has profound implications for cancer therapy. Recently, immunotherapies that activate adaptive immunity have shown unprecedented promise in the clinic, producing durable responses and dramatic increases in survival rate in patients with advanced stage melanoma (84, 119, 121). Consequently, the relationship between cancer and inflammation has now returned to the forefront of clinical oncology.

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“…The abundant clinical and experimental evidence correlating lymphangiogenesis with tumor progression contrasts with reports that lymphangiogenesis in tissue transplantation can promote graft rejection (18), and further confounding the issue are reports suggesting that lymphangiogenesis promotes immune resolution in chronic inflammation (12,13). Therefore, it is likely that lymphatic vessels may serve multiple and complex roles in both the induction and resolution of local immune responses in acute versus chronic inflammation (19).…”

Section: Introductionmentioning

confidence: 99%