Prognostic value of soluble PD-L1 and exosomal PD-L1 in advanced gastric cancer patients receiving systemic chemotherapy

Shin, Kabsoo; Kim, Joori; Park, Sejun; Lee, Myung Ah; Park, Jae Myung; Choi, Myung‐Gyu; Kang, Donghoon; Song, Kyo Young; Lee, Han Hong; Seo, Ho Seok; Lee, Sung Hak; Kim, Bohyun; Kim, Okran; Park, Juyeon; Kang, Nahyeon; Kim, Inho

doi:10.1038/s41598-023-33128-9

Cited by 16 publications

(5 citation statements)

References 50 publications

(43 reference statements)

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“…To the best of our knowledge the values of soluble PD-L1 and PD-1 were not further investigated in association with PFS in PCa. Given the cold immune subtype of prostate tumor, Kaplan Meier analysis in our study revealed shortened PFS correlation with high baseline sPD-L1 values in PCa, as in many other tumors characterized by non-immunologically cold TME such as HCC ( 45 ), gastric cancer ( 46 , 47 ), breast cancer (BC) ( 48 ) glioma ( 41 ) and several NSCLC studies ( 14 , 49 , 50 ).…”

Section: Discussionsupporting

confidence: 52%

Prognostic significance of soluble PD-L1 in prostate cancer

Zvirble,

Survila,

Bosas

et al. 2024

Front. Immunol.

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PurposeThe aim of this study was to assess the role of sPD-L1 and sPD-1 as potential biomarkers in prostate cancer (PCa). The association of the values of these soluble proteins were correlated to the clinical data: stage of disease, Gleason score, biochemical recurrence etc. For a comprehensive study, the relationship between sPD-L1 and sPD-1 and circulating immune cells was further investigated.Methods A total of 88 patients with pT2 and pT3 PCa diagnosis and 41 heathy men were enrolled. Soluble sPD-L1 and sPD-1 levels were measured in plasma by ELISA method. Immunophenotyping was performed by flow cytometry analysis.Results Our study’s findings demonstrate that PCa patients had higher levels of circulating sPD-L1 and sPD-1 comparing to healthy controls (p < 0.001). We found a statistically significant (p < 0.05) relationship between improved progression free survival and lower initial sPD-L1 values. Furthermore, patients with a lower sPD-1/sPD-L1 ratio were associated with a higher probability of disease progression (p < 0.05). Additionally, a significant (p < 0.05) association was discovered between higher Gleason scores and elevated preoperative sPD-L1 levels and between sPD-1 and advanced stage of disease (p < 0.05). A strong correlation (p < 0.05), between immunosuppressive CD4+CD25+FoxP3+ regulatory T cells and baseline sPD-L1 was observed in patients with unfavorable postoperative course of the disease, supporting the idea that these elements influence each other in cancer progression. In addition to the postoperative drop in circulating PD-L1, the inverse relationship (p < 0.05), between the percentage of M-MDSC and sPD-L1 in patients with BCR suggests that M-MDSC is not a source of sPD-L1 in PCa patients.Conclusion Our findings suggest the potential of sPD-L1 as a promising prognostic marker in prostate cancer.

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Section: Discussionsupporting

confidence: 52%

Prognostic significance of soluble PD-L1 in prostate cancer

Zvirble,

Survila,

Bosas

et al. 2024

Front. Immunol.

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“…Findings showed that the low exoPD-L1 group showed a tendency of longer PFS than the high exoPD-L1 group. Importantly, high exoPD-L1 group showed a significantly lower frequency of CD8+ T cells than the low exoPD-L1 group [19]. This indicates that EV-delivered PD-L1 produced by GC cells can interact with PD-1 on infiltrating T cells, leading to the apoptosis and inactivation of T cells.…”

Section: Gc Cells-derived Evs Communicate With Immune Cellsmentioning

confidence: 89%

Extracellular vesicles mediated gastric cancer immune response: tumor cell death or immune escape?

Yang,

Wei,

Wei

2024

Cell Death Dis

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Gastric cancer (GC) is a major global health issue, being the fifth most prevalent cancer and the third highest contributor to cancer-related deaths. Although treatment strategies for GC have diversified, the prognosis for advanced GC remains poor. Hence, there is a critical need to explore new directions for GC treatment to enhance diagnosis, treatment, and patient prognosis. Extracellular vesicles (EVs) have emerged as key players in tumor development and progression. Different sources of EVs carry different molecules, resulting in distinct biological functions. For instance, tumor-derived EVs can promote tumor cell proliferation, alter the tumor microenvironment and immune response, while EVs derived from immune cells carry molecules that regulate immune function and possess tumor-killing capabilities. Numerous studies have demonstrated the crucial role of EVs in the development, immune escape, and immune microenvironment remodeling in GC. In this review, we discuss the role of GC-derived EVs in immune microenvironment remodeling and EVs derived from immune cells in GC development. Furthermore, we provide an overview of the potential uses of EVs in immunotherapy for GC.

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“…A higher level of Exo-PD-L1 was also associated with fewer CD4+ and CD8+ T cells and reduced granzyme B expression in gastric cancer patients, with poorer survival [ 145 ]. This association was not observed with other forms of soluble PD-L1 [ 145 , 146 ], possibly because exosomes express not only PD-L1 molecules but also other immune signalling molecules such as the major histocompatibility complex (MHC). PD-1/PD-L1 can only inhibit the targeted T cells when the binding happens in close proximity to MHC-TCR (T cell receptor) signalling cascades [ 147 , 148 ].…”

Section: Developing Tex As Predictive or Diagnostic Biomarkers For Npcmentioning

confidence: 99%

Unfolding the Complexity of Exosome–Cellular Interactions on Tumour Immunity and Their Clinical Prospects in Nasopharyngeal Carcinoma

Chak,

Kam,

Choi

et al. 2024

Cancers

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Nasopharyngeal carcinoma (NPC) is an epithelial malignancy situated in the posterolateral nasopharynx. NPC poses grave concerns in Southeast Asia due to its late diagnosis. Together with resistance to standard treatment combining chemo- and radiotherapy, NPC presents high metastatic rates and common recurrence. Despite advancements in immune-checkpoint inhibitors (ICIs) and cytotoxic-T-lymphocytes (CTLs)-based cellular therapy, the exhaustive T cell profile and other signs of immunosuppression within the NPC tumour microenvironment (TME) remain as concerns to immunotherapy response. Exosomes, extracellular vesicles of 30–150 nm in diameter, are increasingly studied and linked to tumourigenesis in oncology. These bilipid-membrane-bound vesicles are packaged with a variety of signalling molecules, mediating cell–cell communications. Within the TME, exosomes can originate from tumour, immune, or stromal cells. Although there are studies on tumour-derived exosomes (TEX) in NPC and their effects on tumour processes like angiogenesis, metastasis, therapeutic resistance, there is a lack of research on their involvement in immune evasion. In this review, we aim to enhance the comprehension of how NPC TEX contribute to cellular immunosuppression. Furthermore, considering the detectability of TEX in bodily fluids, we will also discuss the potential development of TEX-related biomarkers for liquid biopsy in NPC as this could facilitate early diagnosis and prognostication of the disease.

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Prognostic value of soluble PD-L1 and exosomal PD-L1 in advanced gastric cancer patients receiving systemic chemotherapy

Cited by 16 publications

References 50 publications

Prognostic significance of soluble PD-L1 in prostate cancer

Prognostic significance of soluble PD-L1 in prostate cancer

Extracellular vesicles mediated gastric cancer immune response: tumor cell death or immune escape?

Unfolding the Complexity of Exosome–Cellular Interactions on Tumour Immunity and Their Clinical Prospects in Nasopharyngeal Carcinoma

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