Evidence map›Paper›PMID 30377565›Full record

ArticleOncoimmunology

Enhancing the immune stimulatory effects of cetuximab therapy through TLR3 signalling in Epstein-Barr virus (EBV) positive nasopharyngeal carcinoma.

Louise Soo Yee Tan, Benjamin Wong, Nagaraja Rao Gangodu, Andrea Zhe Ern Lee, Anthony Kian Fong Liou, Kwok Seng Loh, Hao Li, Ming Yann Lim, Andres M Salazar, Chwee Ming Lim

Open access · goldAbstract read
In one paragraph

Article in Oncoimmunology. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
0.7field-weighted citation impact, top 32% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 12 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 2 countries.

Louise Soo Yee TanDepartment of Otolaryngology-Head and Neck Surgery, National University Health System Singapore, Singapore.
Benjamin WongDepartment of Pathology, National University Health System Singapore, Singapore.
Nagaraja Rao GangoduDepartment of Otolaryngology-Head and Neck Surgery, National University Health System Singapore, Singapore.
Andrea Zhe Ern LeeDepartment of Otolaryngology-Head and Neck Surgery, National University Health System Singapore, Singapore.ORCID 0000-0002-8519-4478
Anthony Kian Fong LiouDepartment of Otolaryngology-Head and Neck Surgery, National University Health System Singapore, Singapore.
Kwok Seng LohDepartment of Otolaryngology-Head and Neck Surgery, National University Health System Singapore, Singapore.
Hao LiDepartment of Otorhinolaryngology, Tan Tock Seng Hospital, Singapore.ORCID 0000-0001-7191-5118
Ming Yann LimDepartment of Otorhinolaryngology, Tan Tock Seng Hospital, Singapore.ORCID 0000-0001-5038-7037
Andres M SalazarOncovir, Inc., Washington, DC, USA.
Chwee Ming LimDepartment of Otolaryngology-Head and Neck Surgery, National University Health System Singapore, Singapore.ORCID 0000-0001-9528-4365
National University Health System · SGTan Tock Seng Hospital · SGNational University of Singapore · SGOncovir (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cetuximab immunotherapy targeting the epidermal growth factor receptor (EGFR) has been used to treat nasopharyngeal cancer (NPC) with some success. Therefore, combining an immune adjuvant to boost the immune microenvironment may improve its clinical efficacy. Herein, we investigate the immune-stimulatory effects of Poly-ICLC (a TLR3 agonist) in enhancing cetuximab-based immunotherapy and correlate these responses with FcɣRIIIa (V158F) or TLR3 single nucleotide polymorphisms (SNPs- L412F and C829T) expressed on immune effector cells. We observed high levels of TLR3 mRNA in NPC cells; and both TLR3 and EGFR expression were unaffected by Poly-ICLC treatment. Cetuximab plus Poly-ICLC significantly enhanced NK-mediated ADCC through up-regulation of CD107a and Granzyme B expression. This effect was independent of FcɣRIIIa-V158F and TLR3-L412F or TLR3-C829T polymorphisms expressed on NK cells. Additionally, IFN-ɣ expression and secretion were doubled following cetuximab plus poly-ICLC treatment; compared to either treatment alone. This effect was independent of TLR3 polymorphisms. Consequentially, adaptive immune responses were also seen with increased DC maturation (CD83), co-stimulatory molecules expression (CD80 and CD86) and increased frequency of EGFR-specific CD8 + T cells following Poly-ICLC treatment. The percentage of CD80+ CD83+ and CD83+ CD86+ DC was highest in the Poly-ICLC plus cetuximab group, compared to either treatment alone. These results demonstrate the effectiveness of Poly-ICLC in enhancing both cetuximab-mediated innate and adaptive anti-tumor immunity against NPC, which is independent of FcɣRIIIa-158, TLR3-L412F or TLR3-C829T polymorphisms. Additionally, Poly-ICLC does not downregulate EGFR expression on NPC cells and hence, will not dampen cetuximab anti-tumor activity.

Indexed as

CetuximabNasopharyngeal carcinoma (NPC)Poly-L-lysine double stranded RNA (Poly-ICLC)polymorphismsToll-like receptor 3 (TLR3)

Identifiers

PMID30377565
PMCPMC6204995
OpenAlexW2889491623

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.