Immunophenotype of T Cells Expressing Programmed Death-1 and Cytotoxic T Cell Antigen-4 in Early Lung Cancer: Local vs. Systemic Immune Response

Kwiecień, Iwona; Skirecki, Tomasz; Polubiec-Kownacka, Małgorzata; Raniszewska, Agata; Domagała‐Kulawik, Joanna

doi:10.3390/cancers11040567

Cited by 18 publications

(12 citation statements)

References 46 publications

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“…These insights, while mostly originating from mouse studies, have meanwhile been validated in specimens of patients with lung and other cancers [136]. In addition, tumor-infiltrating and peripheral blood lymphocytes of NSCLC patients gradually acquire expression of multiple inhibitory receptors (IRs), including programmed cell-death protein (PD)-1, T-cell immunoreceptor with Ig and ITIM domains (TIGITs), lymphocyte-activation gene (LAG)-3, B- and T-lymphocyte attenuator (BTLA), and T-cell immunoglobulin and mucin-domain containing (TIM)-3, that aggravate dysfunctionality [152, 153]. Normally, these appear only transiently on effector T cells, serving as checkpoints to restrain potentially dangerous hyperreactivity [154].…”

Section: Immunopathogenesis Of Lung Cancermentioning

confidence: 99%

Immune Modulation in Lung Cancer: Current Concepts and Future Strategies

Gaissmaier

Christopoulos

2020

Respiration

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Cancer immunotherapy represents the most dynamic field of biomedical research currently, with thoracic immuno-oncology as a forerunner. PD-(L)1 inhibitors are already part of standard first-line treatment for both non-small-cell and small-cell lung cancer, while unprecedented 5-year survival rates of 15–25% have been achieved in pretreated patients with metastatic disease. Evolving strategies are mainly aiming for improvement of T-cell function, increase of immune activation in the tumor microenvironment (TME), and supply of tumor-reactive lymphocytes. Several novel therapeutics have demonstrated preclinical efficacy and are increasingly used in rational combinations within clinical trials. Two overarching trends dominate: extension of immunotherapy to earlier disease stages, mainly as neoadjuvant treatment, and a shift of focus towards multivalent, individualized, mutatome-based antigen-specific modalities, mainly adoptive cell therapies and cancer vaccines. The former ensures ample availability of treated and untreated patient samples, the latter facilitates deeper mechanistic insights, and both in combination build an overwhelming force that is accelerating progress and driving the greatest revolution cancer medicine has seen so far. Today, immune modulation represents the most potent therapeutic modality in oncology, the most important topic in clinical and translational cancer research, and arguably our greatest, meanwhile justified hope for achieving cure of pulmonary neoplasms and other malignancies in the next future.

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Section: Immunopathogenesis Of Lung Cancermentioning

confidence: 99%

Immune Modulation in Lung Cancer: Current Concepts and Future Strategies

Gaissmaier

Christopoulos

2020

Respiration

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“…A higher proportion of CTLA-4 was found in BALF from the lung with lung cancer when compared with the opposite “healthy” lung and peripheral blood (85). In a recent study we found elevated CTL-4 positive lymphocytes in regard to their maturation state (92). Lung cancer environment reflected by BALF was enriched with CTLA-4 positive maturated lymphocytes.…”

Section: Lung Cancer Immunitymentioning

confidence: 79%

“…As shown in our studies, all of the above-mentioned cells are feasible to identify in BALF from the alveolar space adjacent to the tumor (94). Recently we present elevated proportion of PD-1 and CTLA-4 positive cells and expression of these molecules on memory- activated CD8 cells in lung cancer milieu (92). However, the lack of confirmation of predictive value of the findings is the limitation of these studies.…”

Section: Lung Cancer Immunitymentioning

confidence: 99%

New Frontiers for Molecular Pathology

Domagała‐Kulawik

2019

Front. Med.

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Lung cancer remains a serious oncological problem worldwide. The delayed diagnosis and a prevalence of advanced stages in up to 70% of cases at recognition are still observed. Thanks to targeted therapies and immunotherapy a significant progress in achieving prolonged survival in some lung cancer patients is reported. A precise histopathological diagnosis, especially the recognition of adenocarcinoma, and a progress in the methods of clinical staging underlie the proper qualification of patients for a tailored therapy. The deep molecular characteristics of lung cancer in liquid biopsy, for example blood, bronchoalveolar lavage fluid (BALF), cell suspension from needle aspirates, are currently available. The molecular characteristic has recently been extended with molecular aberrations of BRAF, KRAS, MET, ERBB2, RET, NTRK next to the well-known EGFR mutations and ALK, ROS-1 relocation. The present paper discusses the usefulness of adequate pathological methods and molecular testing for the identification of a broad spectrum of predictive biomarkers for a molecular-directed lung cancer therapy. Immunotherapy with immune checkpoint inhibitors (ICIs) is approved in the first line therapy of advanced non-small-cell lung cancer. To date only PD-L1 expression on tumor cells has been found to be a marker of response to ICIs. The efficacy of ICIs as well as the susceptibility to immune-related adverse events are highly individual, so immune biomarkers are widely investigated. The candidates for predictive factors for ICIs immunotherapy include cancer cell antigenicity, presence of regulatory/suppressory molecules on cancer cells, cancer stem cells or on exosomes, and, on the other hand, an immune status of the patient. Cancers with high immune infiltration in the tumor milieu, referred to as “hot” tumors, seem to ensure a better response to ICIs than the “cold” ones. BALF analysis may replace cancer tissue examination, which is of limited access in advanced stages, for the recognition of the nature of immune response in the tumor environment. Tumor mutational burden (TMB) was shown to correlate with a good response to ICIs, especially when combined with other anticancer therapies. The present paper demonstrates the results of recent studies on lung cancer characteristics which bring us closer to the definition of useful prognostic/predictive factors.

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“…This expression is tightly regulated and it remains highly expressed during chronic antigen exposure (49,50). There are very few data about the differential expression of PD-1 in subpopulations of naïve, effector, and memory CD4 + T cells, and most of the data associates PD-1 expression with T cell exhaustion (51)(52)(53). Activated CD4 + T cells play an important role during human CL, acting as an important source of cytokines such as IFN-γ and TNF-α that are associated with lesion healing or disease progression (54,55).…”

Section: Discussionmentioning

confidence: 99%

Programmed Cell Death Ligand (PD-L)-1 Contributes to the Regulation of CD4+ T Effector and Regulatory T Cells in Cutaneous Leishmaniasis

et al. 2020

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Cutaneous Leishmaniasis (CL) affects up to one million people every year and treatments are costly and toxic. The regulation of the host immune response is complex and the knowledge of how CD4 + T cells are activated and maintained during Leishmania infection is still limited. Current therapies aim to target programmed cell death (PD)-1 and programmed cell death ligand (PD-L)-1 in order to boost T cell activity. However, the role of the PD-1/PD-L1 axis during Leishmania infection is still unclear. In this study, we found that patients with active and post-treatment CL displayed different subsets of CD4 + PD-1 + T cells. Accordingly, L. major-infected mice upregulated PD-1 on activated CD4 + T effector cells and PD-L1 on resident macrophages and infiltrating monocytes at the site of infection. L. major-infected Pdl1 −/− mice expressed lower levels of MHCII and higher levels of CD206 on macrophages and monocytes and, more importantly, the lack of PD-L1 contributed to a reduced frequency of CD4 + Ly6C hi T effector cells and an increase of CD4 + Foxp3 + regulatory T cells at the site of infection and in draining lymph nodes. Additionally, the lack of PD-L1 was associated with lower production of IL-27 by infiltrating monocytes and lower levels of the Th1 cytokines IFN-γ and TNF-α produced by CD4 + T effector cells. Pdl1 −/− mice initially exhibited larger lesions despite having a similar parasite load. Our results describe for the first time how the interruption of the PD-1/PD-L1 axis influences the immune response against CL and suggests that this axis regulates the balance between CD4 + Ly6C hi T effector cells and CD4 + Foxp3 + regulatory T cells.

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Immunophenotype of T Cells Expressing Programmed Death-1 and Cytotoxic T Cell Antigen-4 in Early Lung Cancer: Local vs. Systemic Immune Response

Cited by 18 publications

References 46 publications

Immune Modulation in Lung Cancer: Current Concepts and Future Strategies

Immune Modulation in Lung Cancer: Current Concepts and Future Strategies

New Frontiers for Molecular Pathology

Programmed Cell Death Ligand (PD-L)-1 Contributes to the Regulation of CD4+ T Effector and Regulatory T Cells in Cutaneous Leishmaniasis

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