Prognostic relevance of genetic variants involved in immune checkpoints in patients with colorectal cancer

Yoon, Se-Hee; Kang, Byung Woog; Park, Suyeon; Kim, Hye Jin; Park, Jun Seok; Choi, Gyu Seog; Kim, Jong Gwang

doi:10.1007/s00432-016-2196-2

Cited by 14 publications

(13 citation statements)

References 24 publications

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“…Yoon S et al . identified that PD‐1 rs10204525 has an influence on the survival outcomes of the patients with respectable CRC . Sasaki H et al .…”

Section: Discussioncontrasting

confidence: 77%

“…16 Yoon S et al identified that PD-1 rs10204525 has an influence on the survival outcomes of the patients with respectable CRC. 23 Sasaki H et al showed that rs36084323 in the PD-1 GG genotype was correlated with a poor survival of patients of nonsmall-cell lung cancer. 24 However, in our study, the SNPs in PD-1 were not found to be associated with GCs.…”

Section: Discussionmentioning

confidence: 99%

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Polymorphism of the programmed death‐ligand 1 gene is associated with its protein expression and prognosis in gastric cancer

Zhao

Jia

et al. 2018

J of Gastro and Hepatol

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Background and Aim While the incidence and mortality of gastric cancer (GC) remains high, and prognosis of GC remains poor, molecules in programmed death‐1 (PD‐1), programmed death‐ligand 1 (PD‐L1), and programmed death‐ligand 2 (PD‐L2) pathway are promising prognostic biomarker of GC. The polymorphisms on PD‐1, PD‐L1, and PD‐L2 may be associated with their protein expressions and affect the survival of GC patient. Methods Seven hundred fifty‐six GC patients who voluntarily supplied blood samples were enrolled in our study. We genotyped nine polymorphisms on PD‐1, PD‐L1, and PD‐L2, then evaluated the association of the single nucleotide polymorphisms with GC prognosis and analyzed the relationship between the PD‐1, PD‐L1, and PD‐L2 single nucleotide polymorphism genotypes and their protein expression. Results We found that PD‐L1 rs822336 CC genotype was independently associated with a better survival of all GC patients and those without postoperative chemotherapy (hazard ratio [HR] = 0.504, 95% confidence interval [CI] = 0.283–0.897 and HR = 0.385, 95% CI = 0.189–0.786). AA+AG genotype of rs2297136 in 3'UTR of the PD‐L1 was correlated with the protein expression of PD‐L1 protein both in patients overall and those without postoperative chemotherapy (P = 0.013 and P = 0.012). AA+AG genotype of rs2297136 served as an independent factor of better prognosis in patients without postoperative chemotherapy (HR = 0.348, 95% CI = 0.125–0.968). Conclusions Overall, PD‐L1 polymorphisms and protein expression were associated with the prognosis of patients with GC.

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“…Yoon S et al . identified that PD‐1 rs10204525 has an influence on the survival outcomes of the patients with respectable CRC . Sasaki H et al .…”

Section: Discussioncontrasting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Polymorphism of the programmed death‐ligand 1 gene is associated with its protein expression and prognosis in gastric cancer

Zhao

Jia

et al. 2018

J of Gastro and Hepatol

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“…Nevertheless, many other studies have proved associations of rs187084 and rs352140 with numerous immune-related diseases, response to therapies, as well as bacterial and viral infections in populations of both Western and Eastern Eurasian ancestry [20,21,22,23,24,25]. It is also worth noting that the common rs4586 SNP, flanking the promoter of CCL2 gene, which appeared significant for genotype frequencies between our cases and controls (p = 0.0079, OR = 8.5, Table II), was recently found to be significantly correlated with anti-tumour immune reaction in Korean patients with colorectal cancer [26] and associated with the clinical outcome in Japanese individuals with locoregional gastric cancer [27]. Moreover, the TLR2 intergenic polymorphism rs4585282 (previous rs numbers: rs6535939, rs61329579), which was found in our study as significant for genotype frequencies (at p = 0.0000033 or p = 0.0083, depending on the model of association, Table II), was recently indicated as displaying modest associations with some vitiligo subgroups [28], while the T allele of this SNP was previously reported to be associated with pulmonary tuberculosis in a West African but not a European population sample [29].…”

Section: Resultsmentioning

confidence: 55%

Massively parallel targeted resequencing reveals novel genetic variants associated with aspergillosis in paediatric patients with haematological malignancies

Skonieczna¹,

Styczyński²,

Krenska³

et al. 2017

pjp

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This study aimed to find novel genetic variants of susceptibility to aspergillosis in paediatric patients with haematological malignancies. Complete sequences of fifteen genes of human innate immunity (CCL2, CCR2, CD209, CLEC6A, CLEC7A and ten TLR genes) were studied in 40 patients diagnosed with haematological disorders (20 unaffected and 20 affected by aspergillosis). All samples were sequenced with MiSeq (Illumina) and 454 (Roche Diagnostics) technologies. Statistical significance of the differences between studied groups was determined using the twotailed Fisher's exact test. Sixty variants of potential importance were identified, the vast majority of which are located in non-coding parts of the targeted genes. At the threshold of p < 0.000005, one intergenic (TLR2 rs4585282) and one intronic variant (CLEC6A rs12099687) were found significant between the case and control groups for genotype and allele frequencies, respectively. Rs12099687 in CLE-C6A was predicted to constitute an alternative isoform or cryptic splice site, which potentially changes activity of the Dectin-2 protein. Overall, we assume that the two strongest associations reported in this study are expected to be reproducible even in the absence of other evidence, while another twelve associations may be strong enough to justify additional research in larger cohorts.

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“…Interestingly, repeated infusion of recombinant sCD5 protein into wild-type mice reproduced both the immunophenotypic changes and the exacerbated anti-melanoma response, thus ruling out that they could be attributed to putative transgenesis artifacts. From another point of view, genetic variants of immune checkpoint regulators may influence the outcome of cancer patients [64][65][66]. Very recently, two retrospective studies have reported the relevance of nonsynonymous CD5 single nucleotide polymorphisms (rs2241002 C>T, P224>L; rs2229177 C>T, A471>V) in solid and non-solid tumors outcome.…”

Section: Cd5 In Cancer Immunotherapymentioning

confidence: 99%

Exploiting scavenger receptors in cancer immunotherapy: Lessons from CD5 and SR‐B1

et al. 2017

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Scavenger receptors (SRs) are structurally heterogeneous cell surface receptors characterized by their capacity to remove extraneous or modified self-macromolecules from circulation, thus avoiding the accumulation of noxious agents in the extracellular space. This scavenging activity makes SRs important molecules for host defense and homeostasis. In turn, SRs keep the activation of the steady-state immune response in check, and participate as co-receptors in the priming of the effector immune responses when the macromolecules are associated with a threat that might compromise host homeostasis. Therefore, SRs built up sophisticated sensor mechanisms controlling the immune system, which may be exploited to develop novel drugs for cancer immunotherapy. In this review, we focus on the regulation of the anti-tumor immune response by two paradigmatic SRs: the lymphocyte receptor CD5 and the more broadly distributed scavenger receptor class B type 1 (SR-B1). Cancer immunity can be boosted by blockade of SRs working as immune checkpoint inhibitors (CD5) and/or by proper engagement of SRs working as innate danger receptor (SR-B1). Thus, these receptors illustrate both the complexity of targeting SRs in cancer immunotherapy and also the opportunities offered by such an approach. Keywords:Cancer immunotherapy r CD5 r Danger signal r Immune-checkpoint r Scavenger receptor r Scavenger receptor class B type 1 r Toll-like receptors IntroductionThe cancer-immunity cycle can be subverted by tumors at many steps, thus novel therapeutic interventions should be considered for all these possibilities [1]. This cycle starts with the release of tumor antigens and their subsequent capture by professional antigen-presenting cells (mainly, dendritic cells; DCs) for the activation of effector cells of the innate and adaptive immune Correspondence: Dr. Pedro Berraondo e-mail: pberraondol@unav.es system. This is a highly regulated process aimed at maintaining the integrity of the host without inducing significant side effects (e.g., inflammation or autoimmunity) [2]. Tissue homeostasis involves phagocytic processes to remove the excess of native or modified molecules from unviable or stressed cells, as well as from invading microbial agents [3]. Such molecules include lipids, whose intracellular levels should be carefully controlled to sustain proper cell metabolism; endogenous glyco-and lipo-proteins, damaged or * These authors contributed equally to this work. * * These authors are senior co-authors of this work. [4,5]. This phagocytic activity should be coupled to an alarm signal system that awakens other effector mechanisms of the immune system when the tissue damage cannot be controlled by the removal of the endogenous or exogenous molecules. To this end, the immune system has a myriad of specialized soluble or membrane-bound receptors called pattern recognition receptors (PRRs). These PRRs are non-polymorphic, nonclonally distributed, and germ-line encoded receptors recognizing microorganism-associated molecular patterns (MAMPs) -tha...

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Prognostic relevance of genetic variants involved in immune checkpoints in patients with colorectal cancer

Abstract: In conclusion, this results suggest that the genetic predisposition of the host may affect the anti-tumor immune reaction in CRC. The results of this study may also be helpful when selecting targets for novel drug development to promote the anti-tumor immune response.

Cited by 14 publications

References 24 publications

Polymorphism of the programmed death‐ligand 1 gene is associated with its protein expression and prognosis in gastric cancer

Polymorphism of the programmed death‐ligand 1 gene is associated with its protein expression and prognosis in gastric cancer

Massively parallel targeted resequencing reveals novel genetic variants associated with aspergillosis in paediatric patients with haematological malignancies

Exploiting scavenger receptors in cancer immunotherapy: Lessons from CD5 and SR‐B1

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