Increased BTLA and HVEM in gastric cancer are associated with progression and poor prognosis

Lan, Xiuwen; Li, Sen; Gao, Hongyu; Nanding, Abiyasi; Quan, Lina; Yang, Chunyan; Ding, Shaohua; Xue, Yingwei

doi:10.2147/ott.s128825

Cited by 82 publications

(69 citation statements)

References 27 publications

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“…Depending on downstream signaling pathways, BTLA may transmit stimulatory or inhibitory signals possibly accounting for its controversial roles in malignant melanoma, gastric, and gall bladder cancer. [32][33][34][35][36][37] We show that BTLA was expressed on more than 50% of CD8 + T cells isolated from peripheral blood, tumor, and unaffected mucosa although expression was less on TILs compared to T UM . The functional and clinical significance of BTLA expression on TILs and T UM in rectal cancer has to be determined in future studies.…”

Section: Discussionmentioning

confidence: 78%

Localization-associated immune phenotypes of clonally expanded tumor-infiltrating T cells and distribution of their target antigens in rectal cancer

et al. 2019

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The degree and type of T cell infiltration influence rectal cancer prognosis regardless of classical tumor staging. We asked whether clonal expansion and tumor infiltration are restricted to selected-phenotype T cells; which clones are accessible in peripheral blood; and what the spatial distribution of their target antigens is. From five rectal cancer patients, we isolated paired tumor-infiltrating T cells (TILs) and T cells from unaffected rectum mucosa (T UM) using 13-parameter FACS single cell index sorting. TCRαβ sequences, cytokine, and transcription factor expression were determined with single cell sequencing. TILs and T UM occupied distinct phenotype compartments and clonal expansion predominantly occurred within CD8 + T cells. Expanded TIL clones identified by paired TCRαβ sequencing and exclusively detectable in the tumor showed characteristic PD-1 and TIM-3 expression. TCRβ repertoire sequencing identified 49 out of 149 expanded TIL clones circulating in peripheral blood and 41 (84%) of these were PD-1 − TIM-3 −. To determine whether clonal expansion of predominantly tumor-infiltrating T cell clones was driven by antigens uniquely presented in tumor tissue, selected TCRs were reconstructed and incubated with cells isolated from corresponding tumor or unaffected mucosa. The majority of clones exclusively detected in the tumor recognized antigen at both sites. In summary, rectal cancer is infiltrated with expanded distinct-phenotype T cell clones that either i) predominantly infiltrate the tumor, ii) predominantly infiltrate the unaffected mucosa, or iii) overlap between tumor, unaffected mucosa, and peripheral blood. However, the target antigens of predominantly tumorinfiltrating TIL clones do not appear to be restricted to tumor tissue.

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Section: Discussionmentioning

confidence: 78%

Localization-associated immune phenotypes of clonally expanded tumor-infiltrating T cells and distribution of their target antigens in rectal cancer

et al. 2019

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“…4,5 However, in cancer, suppressive immune checkpoints are often hyper-activated to ensure an effective evasion of tumor cells from immune surveillance. 6 These immune checkpoints include in part, the B7/butyrophilinlike receptors such as butyrophilin sub-family 3A/CD277 receptors (BTN3A), 7,8 the B and T lymphocyte attenuator (BTLA) belonging to the B7-like receptors 9,10 and the programmed death protein (PD-1) with its ligands PD-L1 and PD-L2. PD-1/PD-L1 pathways blockade (e.g.…”

Section: Introductionmentioning

confidence: 99%

“…8 On the other hand, the B and T lymphocyte attenuator (BTLA) have been shown to inhibit tumor-specific CD8 + T cell proliferation and their high expression correlates with a shorter survival in some solid tumors mainly of the gastrointestinal tract including gastric cancer. 9,10 Despite considerable efforts, the complete role of these molecules in cancer immunotherapy and the specific role of soluble ectodomains of these receptors remain to be elucidated. Recently, the plasmatic soluble forms of sPD-1 and sPD-L1 have been shown to negatively correlate with survival in myeloma.…”

Section: Introductionmentioning

confidence: 99%

Prognostic significance of circulating PD-1, PD-L1, pan-BTN3As, BTN3A1 and BTLA in patients with pancreatic adenocarcinoma

et al. 2019

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PDAC is one of the most heterogeneous cancers with low chemotherapeutic sensitivity due to a dense stroma, a weak vasculature and significant biological aggressivity. In cancer, suppressive immune checkpoints are often hyper-activated to ensure an effective evasion of tumor cells from immune surveillance. These immune checkpoints include in part, the B7/butyrophilin-like receptors such as butyrophilin sub-family 3A/CD277 receptors (BTN3A), the B and T lymphocyte attenuator (BTLA) belonging to the B7-like receptors and the programmed death protein (PD-1) with its ligand PD-L1. We evaluated the plasma level of these markers in 32 PDAC patients (learning cohort) by ad hoc developed ELISA's and showed that there are highly correlated. We used ROC curves and univariate analysis to characterize their prognostic relevance in these patients and showed that their plasma level can serve as survival predictor. Plasma level thresholds that correlate with less than six months survival were established for sPD-1 (>8.6 ng/ml), sPD-L1 (>0.36 ng/ml), sBTLA (>1.91 ng/ml), sBTN3A1 (>6.98 ng/ml) and pan-sBTN3A (>6.92 ng/ml). These thresholds were applied in independent validation cohort composed by 27 new samples and could efficiently discriminate short versus long PDAC survivors. Our study reveals that monitoring the concentration of soluble forms of inhibitory immune checkpoints in plasma can help predict survival in PDAC patients and therefore improve their treatments.

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“…BTLA is structurally and functionally related to CTLA-4 and PD-1 [15,16]. An augmented BTLA level is associated with the progress and poor prediction of gastric cancer [17]. In addition, PD-L1 overexpression was shown to interfere with cell cycle, cell growth, apoptosis, and carcinogenesis [18].…”

Section: Obesity Pd-l1 and Cancersmentioning

confidence: 99%

Herbal Medicines Attenuate PD-L1 Expression to Induce Anti-Proliferation in Obesity-Related Cancers

Yang

Shih

et al. 2019

Nutrients

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Pro-inflammatory hormones and cytokines (leptin, tumor necrosis factor (TNF)-α, and interleukin (IL)-6) rise in obesity. Elevated levels of hormones and cytokines are linked with several comorbidities such as diabetes, heart disease, and cancer. The checkpoint programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) plays an important role in obesity and cancer proliferation. L-thyroxine (T4) and steroid hormones up-regulate PD-L1 accumulation and promote inflammation in cancer cells and diabetics. On the other hand, resveratrol and other herbal medicines suppress PD-L1 accumulation and reduce diabetic effects. In addition, they induce anti-cancer proliferation in various types of cancer cells via different mechanisms. In the current review, we discuss new findings and visions into the antagonizing effects of hormones on herbal medicine-induced anti-cancer properties.

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Increased BTLA and HVEM in gastric cancer are associated with progression and poor prognosis

Cited by 82 publications

References 27 publications

Localization-associated immune phenotypes of clonally expanded tumor-infiltrating T cells and distribution of their target antigens in rectal cancer

Localization-associated immune phenotypes of clonally expanded tumor-infiltrating T cells and distribution of their target antigens in rectal cancer

Prognostic significance of circulating PD-1, PD-L1, pan-BTN3As, BTN3A1 and BTLA in patients with pancreatic adenocarcinoma

Herbal Medicines Attenuate PD-L1 Expression to Induce Anti-Proliferation in Obesity-Related Cancers

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