High PD-L1/CD274 Expression of Monocytes and Blood Dendritic Cells Is a Risk Factor in Lung Cancer Patients Undergoing Treatment with PD1 Inhibitor Therapy

Riemann, Dagmar; Schütte, Wolfgang; Turzer, Steffi; Seliger, Barbara; Möller, Miriam

doi:10.3390/cancers12102966

Cited by 21 publications

(19 citation statements)

References 53 publications

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“…Importantly, recent studies have shown that blocking PD-L1 on DCs improves DC function and leads to enhanced anticancer T cell immunity [ 57 , 58 ]. Furthermore, the expression of PD-L1 on pDCs has also been associated with the induction of tolerogenic immune responses in different experimental settings [ 59 , 60 ] as well as to bad prognosis in cancer patients [ 61 ]. This argues in favor of a role for the upregulation of PD-L1 on pDCs in the development of an impaired antiviral immune response that we observed in NK cell-depleted, infected/treated mice.…”

Section: Discussionmentioning

confidence: 99%

Immunomodulatory Role of NK Cells during Antiviral Antibody Therapy

Naranjo-Gómez¹,

Cahen²,

Lambour³

et al. 2021

Vaccines

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Monoclonal antibodies (mAbs) are now considered as a therapeutic approach to prevent and treat severe viral infections. Using a mouse retroviral model, we showed that mAbs induce protective immunity (vaccinal effects). Here, we investigated the role of natural killer (NK) cells on this effect. NK cells are effector cells that are crucial to control viral propagation upon mAb treatment. However, their immunomodulatory activity during antiviral mAb immunotherapies has been little studied. Our data reveal that the mAb treatment of infected mice preserves the functional activation of NK cells. Importantly, functional NK cells play an essential role in preventing immune dysfunction and inducing antiviral protective immunity upon mAb therapy. Thus, NK cell depletion in mAb-treated, viral-infected mice leads to the upregulation of molecules involved in immunosuppressive pathways (i.e., PD-1, PD-L1 and CD39) on dendritic cells and T cells. NK cell depletion also abrogates the vaccinal effects induced by mAb therapy. Our data also reveal a role for IFNγ-producing NK cells in the enhancement of the B-cell responses through the potentiation of the B-cell helper properties of neutrophils. These findings suggest that preserved NK cell functions and counts might be required for achieving mAb-induced protective immunity. They open new prospects for improving antiviral immunotherapies.

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Section: Discussionmentioning

confidence: 99%

Immunomodulatory Role of NK Cells during Antiviral Antibody Therapy

Naranjo-Gómez¹,

Cahen²,

Lambour³

et al. 2021

Vaccines

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“…Otherwise, a DC gene signature was strongly associated with improved patients’ OS in NSCLC patients undergoing Atezolizumab therapy (PD-L1 blockade) [ 55 ]. DC counts and their expression of coinhibitory molecules, such as PD-L1, can affect therapy response and patients’ survival; patients undergoing ICI monotherapy and exhibiting a higher PD-L1/CD274 expression of DC subtypes and monocytes, respectively, showed a significantly poorer survival [ 56 ]. Understanding and modulating DC counts and functional activity might help to improve the efficacy of T cell-centric immunotherapies in tumor patients [ 57 ].…”

Section: Discussionmentioning

confidence: 99%

Blood Immune Cell Biomarkers in Lung Cancer Patients Undergoing Treatment with a Combination of Chemotherapy and Immune Checkpoint Blockade

Möller

Turzer

Ganchev

et al. 2022

Cancers

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Although immune checkpoint inhibitor (ICI) therapies have improved the treatment of patients with advanced non-small cell lung cancer (NSCLC), several patients do not achieve durable clinical responses. Biomarkers for the prediction of therapy responses are urgently needed. To identify blood cell parameters correlating with patients’ survival, immune cells from 90 patients with NSCLC undergoing a combination of ICI and chemotherapy were prospectively monitored. At the time point of the first and third antibody administration, complete leukocyte blood count, the percentage of HLA-DRlow monocytes, the percentage of 6-Sulfo LacNAc (slan)+CD16+ non-classical monocytes, and the number of circulating dendritic cell (DC) subtypes, as well as T-, B-, and NK cells were determined by multi-color flow cytometry in peripheral blood. The prognostic value of the immune cell parameters investigated was evaluated by patients’ survival analysis, with progression-free survival (PFS) as the main criterion. A total of 67 patients (74.4%) showed a partial remission or a stable disease, and 35% of patients even survived 12 months and longer. Patients with a neutrophil-to-lymphocyte ratio (NLR) ≥6.1, a frequency of HLA-DRlow monocytes ≥22%, of slan+ non-classical monocytes <0.25% of leukocytes, and/or a sum of myeloid DC (MDC) and plasmacytoid DC (PDC) ≤0.14% of leukocytes had a poorer prognosis. The hazard ratio for PFS was 2.097 (1.208–3.640) for the NLR, 1.964 (1.046–3.688) for HLA-DRlow monocytes, 3.202 (1.712–5.99) for slan+ non-classical monocytes, and 2.596 (1.478–4.56) for the MDC/PDC sum. Patients without any of the four risk factors showed the best PFS. Furthermore, low NK cell counts correlated with shorter PFS (cutoff 200 cells/µL). Female patients had lower baseline NK cell counts and a shorter PFS. Our study confirms the usefulness of blood immune cells as biomarkers for clinical response and survival in NSCLC patients undergoing a combined ICI/chemotherapy.

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“…To our knowledge, the clinical significance of IDO1 expression in monocytes of the peripheral blood of cancer patients has not been reported yet. For PD-L1 expression by monocytes, however, a study in lung cancer patients receiving anti-PD-1 demonstrated that PD-L1 expression was higher on HLA-DR hi monocytes and correlated with low PFS ( 60 ).…”

Section: Discussionmentioning

confidence: 99%

Clinical Relevance of Serum Kyn/Trp Ratio and Basal and IFNγ-Upregulated IDO1 Expression in Peripheral Monocytes in Early Stage Melanoma

et al. 2021

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Immune escape is an early phenomenon in cancer development/progression. Indoleamine 2,3-dioxygenase 1 (IDO1) is a normal endogenous mechanism of acquired peripheral immune tolerance and may therefore be tumor-promoting. This study investigated the clinical relevance of IDO1 expression by immune cells in the lymph nodes and blood and of the serum kynurenine/tryptophan (Kyn/Trp) ratio in 65 systemic treatment naïve stage I-III melanoma patients. Blood samples were collected within the first year of diagnosis. Patients had a median follow-up of 61 months. High basal IDO1 expression in peripheral monocytes and low IFNγ-induced IDO1 upregulation correlated with worse outcome independent from disease stage. Interestingly studied factors were not interrelated. During follow-up, the risk of relapse was 9% (2/22) in the subgroup with high IFNγ-induced IDO1 upregulation in monocytes. In contrast, if IDO1 upregulation was low, relapse occurred in 30% (3/10) of patients with low basal IDO1 expression in monocytes and in 61.5% (8/13) in the subgroup with high basal IDO1 expression in monocytes (Log-Rank test, p=0.008). This study reveals some immune features in the blood of early stage melanoma that may be of relevance for disease outcome. These may offer a target for sub-stratification and early intervention.

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High PD-L1/CD274 Expression of Monocytes and Blood Dendritic Cells Is a Risk Factor in Lung Cancer Patients Undergoing Treatment with PD1 Inhibitor Therapy

Cited by 21 publications

References 53 publications

Immunomodulatory Role of NK Cells during Antiviral Antibody Therapy

Immunomodulatory Role of NK Cells during Antiviral Antibody Therapy

Blood Immune Cell Biomarkers in Lung Cancer Patients Undergoing Treatment with a Combination of Chemotherapy and Immune Checkpoint Blockade

Clinical Relevance of Serum Kyn/Trp Ratio and Basal and IFNγ-Upregulated IDO1 Expression in Peripheral Monocytes in Early Stage Melanoma

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