Tumor Infiltrating Immune Cells and Outcome of Merkel Cell Carcinoma: A Population-Based Study

Sihto, Harri; Böhling, Tom; Kavola, Heli; Koljonen, Virve; Salmi, Marko; Jalkanen, Sirpa; Joensuu, Heikki

doi:10.1158/1078-0432.ccr-11-3020

Cited by 132 publications

(148 citation statements)

References 48 publications

(62 reference statements)

Supporting

Mentioning

133

Contrasting

Unclassified

Order By: Relevance

“…Furthermore, among virus-negative tumors, a subset expressed PD-L1 and these PD-L1-positive tumors harbor a higher mutational burden as compared with PD-L1-negative tumors, which may reflect immune recognition within these tumors [89]. Notably there were also varying grades of TIL within virus-negative tumors and an increased TIL infiltration correlated with improved survival, as has been described for MCC more generally [46,48,89]. These findings indicate that among virus-negative MCCs, tumors with higher mutational burdens have increased immune recognition which may indicate that this subset may be particularly responsive to checkpoint inhibitors as has been similarly described in other cancers [92,93].…”

Section: Virus-negative Mccs and Uv-induced Neoantigensmentioning

confidence: 65%

“…reported that intratumoral FOXP3 expression was not correlated with survival in MCC, a study by Sihto et al indicated that increased FOXP3 expression was associated with improved survival [48]. Therefore, it is unclear whether Treg function is a decisive factor in immune evasion in MCC.…”

Section: T Regulatory Cellsmentioning

confidence: 99%

“…Additional studies have also indicated that MCC TILs, including CD3+, CD8+ T cells, are associated with improved overall and disease-specific survival [47,48]. Furthermore, expression of genes encoding granzyme A, B, H and K, CCL19, lymphocyte activation genes (SLAMF1 and NKG2D) and CD8α are associated with favorable prognoses, independent of stage [46].…”

Section: Review Vandeven and Nghiemmentioning

confidence: 99%

“…The presence of soluble MICA in patient sera has been associated with poor outcome in some cancer types [80] but has not been reported in MCC. Infiltration of NK cells intratumorally has been reported in MCC [48] and the development of tumors despite significant downregulation of MHC-I implies that mechanisms of NK cell evasion are being employed within MCC tumors.…”

Section: Infiltration Of M2 Macrophagesmentioning

confidence: 99%

See 3 more Smart Citations

Rationale For Immune-Based Therapies in Merkel Polyomavirus-Positive and -Negative Merkel Cell Carcinomas

Vandeven

Nghiem

2016

Immunotherapy

View full text Add to dashboard Cite

Merkel cell carcinoma (MCC) is a rare but often deadly skin cancer that is typically caused by the Merkel cell polyomavirus (MCPyV). Polyomavirus T-antigen oncoproteins are persistently expressed in virus-positive MCCs (∼80% of cases), while remarkably high numbers of tumor-associated neoantigens are detected in virusnegative MCCs, suggesting that both MCC subsets may be immunogenic. Here we review mechanisms by which these immunogenic tumors evade multiple levels of host immunity. Additionally, we summarize the exciting potential of diverse immunebased approaches to treat MCC. In particular, agents blocking the PD-1 axis have yielded strikingly high response rates in MCC as compared with other solid tumors, highlighting the potential for immune-mediated treatment of this disease.

show abstract

Section: Virus-negative Mccs and Uv-induced Neoantigensmentioning

confidence: 65%

Section: T Regulatory Cellsmentioning

confidence: 99%

Section: Review Vandeven and Nghiemmentioning

confidence: 99%

Section: Infiltration Of M2 Macrophagesmentioning

confidence: 99%

See 2 more Smart Citations

Rationale For Immune-Based Therapies in Merkel Polyomavirus-Positive and -Negative Merkel Cell Carcinomas

Vandeven

Nghiem

2016

Immunotherapy

View full text Add to dashboard Cite

show abstract

“…The link between survival of patients with MCC and the immune system suggests that agents that promote antitumor The primary analysis population consisted of immunocompetent patients, while the overall population included both immunocompetent and immunocompromised patients. immune responses may be a beneficial treatment option for patients with MCC [20,21,33,34]. One potential mechanism used by MCC to evade the immune system is the upregulation of immune checkpoint regulators, such as PD-L1 [23].…”

Section: Discussionmentioning

confidence: 99%

Real-world treatment outcomes in patients with metastatic Merkel cell carcinoma treated with chemotherapy in the USA

et al. 2017

View full text Add to dashboard Cite

aim: This retrospective study of patients in the USA with metastatic Merkel cell carcinoma (mMCC) aimed to assess patient responses to second-line and later (2L+) and first-line (1L) chemotherapy. Patients & methods: Out of 686 patients with MCC identified in The US Oncology Network, 20 and 67 patients with mMCC qualified for the 2L+ and 1L study, respectively; the primary analysis population was restricted to immunocompetent patients. Results: In the 2L+ primary analysis population, objective response rate (ORR) was 28.6%, median duration of response (DOR) was 1.7 months and median progression-free survival was 2.2 months. In the 1L primary analysis population, ORR was 29.4%, median DOR was 6.7 months and median progression-free survival was 4.6 months. conclusion: The low ORR and brief DOR underscore the need for novel therapies. Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer that occurs most frequently in elderly and immunocompromised patients [1][2][3]. There are approximately 1500 cases of MCC per year in the USA, and the incidence has dramatically increased over the last 20 years [4]. MCC typically presents as painless growths that are clinically unremarkable in appearance and are usually found on sun-exposed areas, such as the head and neck [2,3]. These tumors grow rapidly and tend to metastasize early and frequently to local regions of the body, leading to a relatively poor prognosis with this aggressive disease [2,3,5]. Among patients diagnosed with local or regional disease, the reported rates of recurrence range from 43 to 48% [6,7]. The 5-year overall survival (OS) rate is 40% [1] and the mortality rate with MCC is greater than that with other skin cancers, including melanoma [4].Recently, avelumab, a human IgG1 anti-programmed death-ligand 1 (PD-L1) monoclonal antibody, was approved by the US FDA as the first and only approved treatment for patients with metastatic MCC (mMCC) [8]. Before this approval, there was no evidence-based standard therapeutic regimen for mMCC. The National Comprehensive Cancer Network treatment guidelines for mMCC [9] are based on those used for small cell lung cancer, as both are aggressive and poorly differentiated cancers [10]. Treatments typically include platinum agents, such as carboplatin or cisplatin with or without etoposide or topotecan, and are associated with high toxicity [9,11]. Although MCC is generally considered a chemosensitive tumor, responses to chemotherapy in metastatic disease are For reprint orders, please contact: reprints@futuremedicine.com

show abstract

Patterns of Tumor-Infiltrating Lymphocytes Used to Distinguish Primary Cutaneous Squamous Cell Carcinomas That Metastasize

et al. 2023

View full text Add to dashboard Cite

show abstract

Tumor Infiltrating Immune Cells and Outcome of Merkel Cell Carcinoma: A Population-Based Study

Cited by 132 publications

References 48 publications

Rationale For Immune-Based Therapies in Merkel Polyomavirus-Positive and -Negative Merkel Cell Carcinomas

Rationale For Immune-Based Therapies in Merkel Polyomavirus-Positive and -Negative Merkel Cell Carcinomas

Real-world treatment outcomes in patients with metastatic Merkel cell carcinoma treated with chemotherapy in the USA

Patterns of Tumor-Infiltrating Lymphocytes Used to Distinguish Primary Cutaneous Squamous Cell Carcinomas That Metastasize

Contact Info

Product

Resources

About