Chemotherapy treatment is associated with altered PD-L1 expression in lung cancer patients

Rojkó, Lívia; Reiniger, Lilla; Téglási, Vanda; Fábián, Katalin; Pipek, Orsolya; Vágvölgyi, Attila; Acsády, László; Fillinger, János; Kajdácsi, Zita; Tı́már, József; Döme, Balázs; Szállási, Zoltán; Moldvay, Judit

doi:10.1007/s00432-018-2642-4

Cited by 64 publications

(56 citation statements)

References 20 publications

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“…It has already been proven that chemotherapy can change the expression level of PD‐1, but the direction of this change depends on the cell line and chemotherapeutic agent . Moreover, a recent study investigated the expression of PD‐1 and PD‐L1 before and after platinum‐based neoadjuvant chemotherapy in lung cancer patients and found that only PD‐L1 expression decreased significantly after chemotherapy . Conversely, consistent with our study, some studies found opposite results.…”

Section: Discussionsupporting

confidence: 89%

Assessment of the expression of the immune checkpoint molecules PD‐1, CTLA4, TIM‐3 and LAG‐3 across different cancers in relation to treatment response, tumor‐infiltrating immune cells and survival

Guan

Yang

et al. 2019

Intl Journal of Cancer

129

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Immune checkpoint molecules have been identified as crucial regulators of the immune response, which motivated the emergence of immune checkpoint‐targeting therapeutic strategies. However, the prognostic significance of the immune checkpoint molecules PD‐1, CTLA4, TIM‐3 and LAG‐3 remains controversial. The aim of our study was to conduct a systematic assessment of the expression of these immune checkpoint molecules across different cancers in relation to treatment response, tumor‐infiltrating immune cells and survival. Oncomine and PrognoScan database analyses were used to investigate the expression levels and prognostic values of these immune checkpoint molecule genes across various cancers. Then, we used Kaplan–Meier plotter to validate the associations between the checkpoint molecules and cancer survival identified in the PrognoScan analysis. TIMER analysis was used to evaluate immune cell infiltration data from The Cancer Genome Atlas. Finally, we used Gene Expression Profiling Interactive Analysis to investigate the prognostic value of these four checkpoint molecules and assess the correlations between these four checkpoint molecules and genetic markers. These immune checkpoint molecules may potentially serve as prognostic factors and therapeutic targets in breast cancer, ovarian cancer and lung cancer. The prognostic roles of these checkpoint molecules varied greatly across cancers, which implied a noteworthy amount of heterogeneity among tumors, even within the same molecular subtype. In addition, the expression patterns of these checkpoint molecules were closely associated with treatment response and provided some useful direction when choosing chemotherapeutic drugs. These findings enhance our understanding of these checkpoints in cancer treatment and identify strategies to promote synergistic activities in the context of other immunotherapies.

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Section: Discussionsupporting

confidence: 89%

Assessment of the expression of the immune checkpoint molecules PD‐1, CTLA4, TIM‐3 and LAG‐3 across different cancers in relation to treatment response, tumor‐infiltrating immune cells and survival

Guan

Yang

et al. 2019

Intl Journal of Cancer

129

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“…Similar observations were shown in lung cancer patients, with different histological characteristics and treated with cisplatin or carboplatin-derived chemotherapy [120]. In NSCLC patients treated with paclitaxel/carboplatin/bevacizumab, proliferating peripheral blood CD8 + T cells express a higher level of PD-1 and CTLA-4 compared to non-proliferating CD8 + T cells [110].…”

Section: Platinum Derivatives and Immune Checkpointssupporting

confidence: 78%

Platinum Derivatives Effects on Anticancer Immune Response

et al. 2019

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Along with surgery and radiotherapy, chemotherapeutic agents belong to the therapeutic arsenal in cancer treatment. In addition to their direct cytotoxic effects, these agents also impact the host immune system, which might enhance or counteract their antitumor activity. The platinum derivative compounds family, mainly composed of carboplatin, cisplatin and oxaliplatin, belongs to the chemotherapeutical arsenal used in numerous cancer types. Here, we will focus on the effects of these molecules on antitumor immune response. These compounds can induce or not immunogenic cell death (ICD), and some strategies have been found to induce or further enhance it. They also regulate immune cells' fate. Platinum derivatives can lead to their activation. Additionally, they can also dampen immune cells by selective killing or inhibiting their activity, particularly by modulating immune checkpoints' expression.Cell death is characterized by morphological alterations that have been historically used by The Nomenclature Committee on Cell Death (NCCD) to classify this cellular process into three different forms: type I or apoptosis, type II or autophagy, and type III or necrosis. Although limited, this morphological classification remains widely used, independently of essential molecular aspects of the cell death process. New NCCD classifications focus on molecular mechanisms and on the biochemistry of intracellular signalization effectors. Currently, it is clear that connections and overlaps exist between the different types of cell death. The majority of chemotherapeutic drugs are known to induce apoptosis or necrosis. Engagement of a particular type of cell death depends on the stress type, interaction between induction factors, genetic cell background, organelle content and enzymatic proteins arsenal [3,4].The action of chemotherapy relies not only on its cytotoxic effect on cancer cells, but also on its ability to affect immune cells.

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“…Interestingly, PD‐L1 expression via the MAPK pathway was reported in cell lines after low‐dose chemotherapy (paclitaxel and cisplatin) (Gong et al, ; Qin, Liu, Zhou, & Wang, ). However, this effect might not translate to the clinical setting, where PD‐L1 levels have been found to decrease, increase or remain unchanged after platinum‐based chemotherapy (Rojkó et al, ). This effect remains of interest, given that drugs such as cisplatin are recommended by the National Comprehensive Cancer Network (NCCN) for cases of unresectable or metastatic HNSCC, and immune checkpoint therapy targeting the PD‐1:PD‐L1 axis is currently approved only after progression following chemotherapy with platinum‐based drugs (Adelstein et al, ).…”

Section: Pd‐l1 In Cancermentioning

confidence: 99%

An update of knowledge on PD‐L1 in head and neck cancers: Physiologic, prognostic and therapeutic perspectives

et al. 2019

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Programmed cell death‐ligand 1 (PD‐L1) is a transmembrane protein that acts as a co‐inhibitory factor in the immune response. Its receptor, programmed cell death protein 1 (PD‐1), is found on immune cells, where binding to PD‐L1 can reduce the proliferation of PD‐1‐positive cells, inhibit their cytokine secretion and induce apoptosis. PD‐L1 in immune‐privileged tissue plays a crucial role in peripheral tolerance. PD‐L1 can be overexpressed in various malignancies, including oral squamous cell carcinoma, where it can attenuate the host immune response to tumour cells and has been associated with a worse prognosis. Monoclonal antibody therapies targeting the PD‐1:PD‐L1 axis have shown initial promise, but further research is needed to identify which patients will benefit. We provide an update of knowledge on PD‐L1, including its structure, function and regulation. We also review studies on the overexpression of PD‐L1 in cancer, specifically oral squamous cell carcinoma, and explore its potential value as a therapeutic target.

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Chemotherapy treatment is associated with altered PD-L1 expression in lung cancer patients

Cited by 64 publications

References 20 publications

Assessment of the expression of the immune checkpoint molecules PD‐1, CTLA4, TIM‐3 and LAG‐3 across different cancers in relation to treatment response, tumor‐infiltrating immune cells and survival

Assessment of the expression of the immune checkpoint molecules PD‐1, CTLA4, TIM‐3 and LAG‐3 across different cancers in relation to treatment response, tumor‐infiltrating immune cells and survival

Platinum Derivatives Effects on Anticancer Immune Response

An update of knowledge on PD‐L1 in head and neck cancers: Physiologic, prognostic and therapeutic perspectives

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