Peripheral changes in immune cell populations and soluble mediators after anti-PD-1 therapy in non-small cell lung cancer and renal cell carcinoma patients

AbstractPatients with non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC) have shown benefit from anti-PD-1 therapies. However, not all patients experience tumor shrinkage, durable responses or prolonged survival, demonstrating the need to find response markers. In blood samples from NSCLC and RCC patients obtained before and after anti-PD-1 treatment, we studied leukocytes by complete blood cell count, lymphocyte subsets using flow cytometry and plasma concentration of nine soluble mediators, in order to find predictive biomarkers of response and to study changes produced after anti-PD-1 therapy. In baseline samples, discriminant analysis revealed a combination of four variables that helped differentiate stable disease-response (SD-R) from progressive disease (PD) patients: augmented frequency of central memory CD4+ T cells and leukocyte count was associated with response while increased percentage of PD-L1+ natural killer cells and na ïve CD4+ T cells was associated with lack of response. After therapy, differential changes between responders and non-responders were found in leukocytes, T cells and TIM-3+ T cells. Patients with progressive disease showed an increase in the frequency of TIM-3 expressing CD4+ and CD8+ T cells, whereas SD-R patients showed a decrease in these subsets. Our findings indicate that a combination of immune variables from peripheral blood  (PB) could be useful to distinguish response groups in NSCLC and RCC patients tr...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research

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varam To elucidate the role of immune cell infiltration as a prognostic signature in solid tumors, we analyzed immune-function-related genes from four publicly available single-cell RNA-Seq data sets and twenty bulk tumor RNA-Seq data sets from The Cancer Genome Atlas (TCGA). Unsupervised clustering of pan-cancer transcriptomic signature showed two major immune function types: one related to NK-, T-, and B-cell functions and the other related to monocyte, macrophage, dendritic cell, and Toll-like receptor functions. Kaplan–Meier analysis showed differential prognosis of these two groups, dependent on the canc...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Immunotherapy directed at the programmed cell death-1 receptor (PD-1) or its ligand PD-L1 has proven effective in solid malignancies such as melanoma, non-small cell lung cancer (NSCLC), urothelial cancer, renal cell carcinoma, and head and neck cancer. Compared with cytotoxic chemotherapy, radiotherapy, or molecular targeted agents, immunotherapy is an innovative strategy for treating malignancies, with durable clinical responses and manageable adverse events. Thymic carcinomas are extremely rare, constituting only 0.06% of all malignancies, are much more aggressive tumours than thymomas and have a worse prognosis. Nowada...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Cancer immunotherapy is a success story of translational medicine that has led to improved survival in patients with different difficult-to-treat types of cancer, such as metastasized melanoma, non-small cell lung cancer or renal cell carcinoma. These novel therapeutic agents exert their antitumor effects by activating the patients' immune system against cancer cells. Immunotherapy can be divided into active agents, such as anti-tumour vaccines or adoptive T-cell transfer, and passive immunotherapies like monoclonal antibodies, checkpoint inhibitors, cytokine therapy, bispecific T-cell engagers.
Source: International Journal of Cardiology - Category: Cardiology Authors: Source Type: research
Abstract Brain metastasis (BM) is associated with a poor prognosis, with the typical overall survival rate ranging from weeks to months in the absence of treatment. Although the concept of immune privilege in the central nervous system has eroded over time, the advent of immunotherapy has opened a new set of potential therapeutic options for patients with BM. Recently, immunotherapy has been demonstrated to confer survival advantages to patients with multiple malignancies commonly associated with BMs. Data from a number of clinical trials have demonstrated that immune checkpoint inhibitors are effective for patien...
Source: International Journal of Oncology - Category: Cancer & Oncology Authors: Tags: Int J Oncol Source Type: research
Use of immune checkpoint blockade has resulted in improved overall survival (OS) in patients with multiple solid cancers, including but not limited to, advanced melanoma, non-small cell lung cancer, urothelial cancer and renal cell carcinoma [1 –4]. Not all patients experience benefit from immunotherapy (and may experience immunotherapy-associated toxicities needlessly), highlighting the need for better patient selection. Reports have suggested that programmed cell death ligand 1 (PD-L1) immunohistochemistry, T-cell infiltration levels, T-cell receptor clonality, gut microbiome composition [5], gene expression signat...
Source: Cancer Treatment Reviews - Category: Cancer & Oncology Authors: Tags: Hot Topic Source Type: research
Conclusion: Serum kyn/trp ratio could have both prognostic and predictive values in patients with solid tumor treated with immunotherapy, probably reflecting a primary immune-resistant mechanism regardless of the primary tumor histology. Its relative weight is significantly related to gender, site of metastasis, NSCLC, and squamous histology, although these suggestive data need to be confirmed in larger studies.
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Immunotherapy enhances a patient's own immune system to fight against malignancy and has become increasingly popular during the last decade. Tumor cells can escape destruction by the patient's immune system by overexpression of immunosuppressive molecules such as cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), programmed cell death-1 (PD-1) receptor, and its ligand PD-L1. Immunotherapy agents target these inhibitors and basically reactivate the cytotoxic lymphocytes to destroy the tumor cells. Immunotherapy agents currently are FDA-approved for advanced malignancies including melanoma, Hodgkin lymphoma, head and neck...
Source: Contemporary Diagnostic Radiology - Category: Radiology Tags: ARTICLE Source Type: research
ConclusionsCurrent clinical trials are exploring combination therapy and novel treatment strategies beyond immune checkpoint therapies and vaccine therapy such as CAR T cells. There is also an effort to establish synergy between immunotherapy and current standard of care. Furthermore, recent advances in personalized neoantigen vaccines suggest a shift towards personalized, patient-specific GBM treatment.
Source: Journal of Neuro-Oncology - Category: Cancer & Oncology Source Type: research
ConclusionsWe find sufficient cause to suggest that the predictive clinical value of TMB should not be overstated or oversimplified. While it is readily quantified, TMB is at best a limited surrogate biomarker of immunotherapy response. The data do not support isolated use of TMB in renal cell carcinoma.
Source: Genome Medicine - Category: Genetics & Stem Cells Source Type: research
Conclusions: Sebaceous carcinoma currently has few effective adjuvant treatment options. The expression of PD-1, PD-L1, and PD-L2 on infiltrating immune cells and PD-L2 on tumor cells restrains T-cells from full activation and proliferation, therefore limiting the antitumor effect of T-cells, tipping the balance toward unopposed tumor progression. Consequently, PD-1 or PD-L1 inhibitors may have a role in sebaceous carcinoma treatment. Given the prevalence of PD-L2 expression in sebaceous carcinoma and the lack of PD-L2 blockade therapy available, PD-1 blockade may provide benefit over PD-L1 inhibitors. PD-1 blockade in c...
Source: Ophthalmic Plastic and Reconstructive Surgery - Category: Opthalmology Tags: Original Investigations Source Type: research
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