Brief in vitro IL-12 conditioning of CD8  + T Cells for anticancer adoptive T cell therapy
AbstractCancer immunotherapy represents a potential treatment approach through non-specific and specific enhancement of the immune responses. Adoptive cell therapy (ACT) is a potential modality of immunotherapy that depends on harvesting T cells from the tumor-bearing host, activating them in vitro and infusing them back to the same host. Several cytokines, in particular IL-2, IL-7 and IL-15, have been used to enhance survival T cells in vitro. Although effective, conditioning of T cells in vitro with these cytokines requires long-term culture which results in the loss of expression of their trafficking receptors mainly CD...
Source: Cancer Immunology, Immunotherapy - September 8, 2021 Category: Cancer & Oncology Source Type: research

Sex-specific hormone changes during immunotherapy and its influence on survival in metastatic renal cell carcinoma
AbstractRenal cell carcinoma (RCC) is a highly vascularized and immunogenic tumor, being an ideal candidate for checkpoint blockade-based immunotherapy. Accordingly, checkpoint inhibitors have demonstrated clinical efficacy in patients with metastatic RCC (mRCC). Sex-specific differences in cancer immunotherapy may be explained by the interaction of sex hormone signaling, genetic and environmental factors, affecting the innate and adaptive immune response in men and women in different ways. The aim of this prospective study was to monitor for the first time changes in sex hormones including luteinizing hormone (LH), follic...
Source: Cancer Immunology, Immunotherapy - September 8, 2021 Category: Cancer & Oncology Source Type: research

Immune modulating activity of the CHK1 inhibitor prexasertib and anti-PD-L1 antibody LY3300054 in patients with high-grade serous ovarian cancer and other solid tumors
ConclusionsPrexasertib in combination with PD-L1 blockade was tolerable and demonstrated preliminary activity inCCNE1-amplified HGSOC with evidence of cytotoxic T-cell activation in patient blood samples.Trial registrationClinicalTrials.gov identifier: NCT03495323. Registered April 12, 2018. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - September 8, 2021 Category: Cancer & Oncology Source Type: research

Simultaneously target of normal and stem cells-like gastric cancer cells via cisplatin and anti-CD133 CAR-T combination therapy
AbstractCD133  + cancer stem cells mediate chemoresistance in multiple aggressive cancers, and anti-CD133 chimeric antigen receptor T (CAR-T) cells are designed to selectively target cisplatin-resistant gastric cancer stem cells in this investigation. The relative CD133 expression was detected in gastric canc er patients before and after cisplatin treatment. Anti-CD133 CAR-T cells were incubated with cisplatin-exposed CD133+ BGC-823 cells to evaluate the killing efficacy. At the same time, the canonical T cell activation markers were assayed by fluorescence-activated cell sorting, and the functional cytokine ...
Source: Cancer Immunology, Immunotherapy - September 8, 2021 Category: Cancer & Oncology Source Type: research

Immune checkpoint inhibitors-associated pericardial disease: a systematic review of case reports
AbstractTreatment with immune checkpoint inhibitors (ICIs) can be complicated by cardiovascular toxicity, including pericardial disease. To date, no prospective studies specifically investigated the optimal treatment of ICI-associated pericardial disease, and the available evidence is based on case reports and series only. We performed a systematic review of case reports and series including 20 publications for a total of 28 cases of ICI-associated pericardial disease. In this review, pericardial disease was reversible in the majority of cases (75%), although 2 deaths were reported. The majority of cases were life-threaten...
Source: Cancer Immunology, Immunotherapy - September 8, 2021 Category: Cancer & Oncology Source Type: research

TIGIT promotes CD8+T cells exhaustion and predicts poor prognosis of colorectal cancer
This study aimed at identifying the function of TIGIT in colorectal cancer. Patients with colorectal cancer showed significantly higher TIGIT+CD8+T cell infiltration in tumor tissues, metastases compared with paired PBMC and normal tissues through flow cytometry. TIGIT+CD8+T cells showed an exhausted phenotype and expressed low levels of killer cytokines IFN- γ, IL-2, TNF-α. In addition, more inhibitory receptors such as PD-1, LAG-3, and TIM-3 were expressed on the surface of TIGIT+CD8+T cells. TGF- β1 could promote the expression of TIGIT and inhibit CD8+T cell function in vitro. Moreover, the accumulatio...
Source: Cancer Immunology, Immunotherapy - September 8, 2021 Category: Cancer & Oncology Source Type: research

Prognostic value of PD-L1 combined positive score in patients with upper tract urothelial carcinoma
ConclusionsA PD-L1 CPS  ≥ 10 in UTUC was associated with adverse pathological features and independently predicted worse cancer-specific and overall survival. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - September 8, 2021 Category: Cancer & Oncology Source Type: research

Phase I/II clinical trial of adoptive cell transfer of sorted specific T cells for metastatic melanoma patients
In conclusion, we demonstrated the feasibility and safety of ACT with multimer-sorted Melan-A and MELOE-1 specific T cells to metastatic melanoma patients. The clinical efficacy of such therapeutic strategy could be further enhanced by the selection of highly reactive T-cells, based on PD-1 and TIGIT co-expression, and a combination with ICI, such as anti-PD-1. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - September 8, 2021 Category: Cancer & Oncology Source Type: research

Tumor morphology and location associate with immune cell composition in pleomorphic sarcoma
ConclusionsOur study provides an immune-based analysis of the tumor microenvironment in UPS patients and describes the different composition of tumor infiltrating lymphocytes based on size and tumor depth. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - September 8, 2021 Category: Cancer & Oncology Source Type: research

Correction to: Cancer testis antigen Cyclin A1 harbors several HLA ‑A*02:01‑restricted T cell epitopes, which are presented and recognized in vivo
A correction to this paper has been published: https://doi.org/10.1007/s00262-021-02977-6 (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - September 8, 2021 Category: Cancer & Oncology Source Type: research

Combination therapy for hepatocellular carcinoma with diacylglycerol kinase alpha inhibition and anti-programmed cell death-1 ligand blockade
We examined the effects of a DGKα inhibitor (DGKAI) on liver cancer cell proliferation and cytokine production by immune cells in vitro and on tumorigenesis and host immunity in a hepatocellular carcinoma (HCC) mouse model. Oral DGKAI significantly suppressed tumor growth and prolonged survival in model mice. Tumor infiltration of T cells and dendritic cells was also enhanced in mice treated with DGKAI, and the production of cytokines and cytotoxic molecules by CD4+ and CD8+ T cells was increased. Depletion of CD8+ T cells reduced the effect of DGKAI. Furthermore, interferon- γ stimulation augmented the express...
Source: Cancer Immunology, Immunotherapy - September 5, 2021 Category: Cancer & Oncology Source Type: research

MAIT cells numbers and frequencies in patients with acute myeloid leukemia at diagnosis: association with cytogenetic profile and gene mutations
AbstractHarnessing or monitoring immune cells is actually a major topic in pre-clinical and clinical studies in acute myeloid leukemia (AML). Mucosal-Associated Invariant T cells (MAIT) constitute one of the largest subset of innate-like, cytotoxic T cell subsets in humans. Despite some papers suggesting a role for MAIT cells in cancer, their specific involvement remains unclear, especially in myeloid malignancies. This prospective monocentric study included 216 patients with a newly diagnosed AML. Circulating MAIT cells were quantified by flow cytometry at diagnosis and during intensive chemotherapy. We observed that circ...
Source: Cancer Immunology, Immunotherapy - September 3, 2021 Category: Cancer & Oncology Source Type: research

Transcriptome of CD8+ tumor-infiltrating T cells: a link between diabetes and colorectal cancer
AbstractThere is an increased risk of colorectal cancer (CRC) development in patients with non-insulin-dependent type 2 diabetes. CD8+ T cells have been implicated in diabetes and are crucial for anti-tumor immunity. However, transcriptomic profiling for CD8+ T cells from CRC diabetic patients has not been explored. We performed RNA sequencing and compared transcriptomic profiles of CD8+ tumor-infiltrating T lymphocytes (CD8+ TILs) in CRC diabetic patients with CRC nondiabetic patients. We found that genes associated with ribogenesis, epigenetic regulations, oxidative phosphorylation and cell cycle arrest were upregul...
Source: Cancer Immunology, Immunotherapy - August 12, 2021 Category: Cancer & Oncology Source Type: research

Correction to: Transcriptome of CD8+ tumor-infiltrating T cells: a link between diabetes and colorectal cancer
A correction to this paper has been published: https://doi.org/10.1007/s00262-021-02903-w (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - August 12, 2021 Category: Cancer & Oncology Source Type: research

Effect of HLA genotype on intravesical recurrence after bacillus Calmette –Guérin therapy for non-muscle-invasive bladder cancer
This study aimed to reveal the effects of zygosity on human leukocyte antigen (HLA) genes and individual HLA genotypes on intravesical recurrence after intravesical BCG therapy for N MIBC. This study included Japanese patients who had received intravesical BCG for NMIBC. HLA genotyping of HLA-A, B, C, and DRB1 was performed. The effect of HLA zygosity and HLA genotype on intravesical recurrence was evaluated. Among 195 patients, those homozygous for the HLA-B supertype were more likely than those heterozygous for the HLA-B supertype to experience intravesical recurrence by univariate analysis (hazard ratio [HR], 95% confid...
Source: Cancer Immunology, Immunotherapy - August 11, 2021 Category: Cancer & Oncology Source Type: research

Anti-PD-(L)1 for KRAS-mutant advanced non-small –cell lung cancers: a meta-analysis of randomized–controlled trials
AbstractPurposeThe most frequent mutation in advanced non-small –cell lung cancer (NSCLC), Kirsten rat-sarcoma viral oncogene (KRAS) is found in 20 –25% of these patients’ tumors. While phase III trials on therapies targetingKRAS, especiallyKRASG12C, are ongoing, the clinical efficacy of anti-programmed death protein-1 (PD-1) or its ligand (PD-L1) againstKRAS-mutant NSCLCs remains a topic of debate.MethodsThis meta-analysis examined randomized-trial data comparing first- or second-line anti-PD-(L)1 with or without chemotherapy vs. chemotherapy alone for advancedKRAS-mutant NSCLCs. Outcome measures include...
Source: Cancer Immunology, Immunotherapy - August 10, 2021 Category: Cancer & Oncology Source Type: research

The role of S100A9 in the interaction between pancreatic ductal adenocarcinoma cells and stromal cells
ConclusionsPSCs stimulated PDAC cells to secrete S100A9, which acts as a chemoattractant to attract circulatory monocytes into cancer microenvironment and induces expression of PD-L1 on macrophages. High expression of S100A9 and PD-L1 was associated with worse overall survival in a cohort of patients with PDAC. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - August 10, 2021 Category: Cancer & Oncology Source Type: research

Factors associated with treatment response to CD19 CAR-T therapy among a large cohort of B cell acute lymphoblastic leukemia
AbstractCD19-targeted chimeric antigen receptor (CAR) T cell therapy has demonstrated striking responses among B cell acute lymphoblastic leukemia (B-ALL), but analyses of potential factors associated with poor response and relapse are lacking. Here, we summarize the long-term follow-up of 254 B-ALL treated with CD19 CAR-T cells from 5 clinical trials (NCT03173417, NCT02546739, and NCT03671460 retrospectively registered on May 23, 2017, March 1, 2018, and September 7, 2018, respectively, atwww.clinicaltrials.gov; ChiCTR-ONC-17012829, and ChiCTR1800016541 retrospectively registered on September 28, 2017, and June 7, 2018, a...
Source: Cancer Immunology, Immunotherapy - August 7, 2021 Category: Cancer & Oncology Source Type: research

Chemotherapy: a double-edged sword in cancer treatment
AbstractChemotherapy is a well-known and effective treatment for different cancers; unfortunately, it has not been as efficient in the eradication of all cancer cells as been expected. The mechanism of this failure was not fully clarified, yet. Meanwhile, alterations in the physiologic conditions of the tumor microenvironment (TME) were suggested as one of the underlying possibilities. Chemotherapy drugs can activate multiple signaling pathways and augment the secretion of inflammatory mediators. Inflammation may show two opposite roles in the TME. On the one hand, inflammation, as an innate immune response, tries to suppr...
Source: Cancer Immunology, Immunotherapy - August 5, 2021 Category: Cancer & Oncology Source Type: research

Telomerase-based GX301 cancer vaccine in patients with metastatic castration-resistant prostate cancer: a randomized phase II trial
AbstractDebate is around the optimal immunization regimen for cancer vaccines since too intense vaccination schedules may exhaust reactive lymphocytes. GX301 is a telomerase-based cancer vaccine whose safety and immunological effects were tested in a phase I trial applying an eight administrations schedule. Main objective of this study was to comparatively analyse safety and immunological response to three GX301 regimens in metastatic castration-resistant prostate cancer patients with response/disease stability after docetaxel chemotherapy. This was a multicentre, randomized, parallel-group, open-label trial registered wit...
Source: Cancer Immunology, Immunotherapy - August 5, 2021 Category: Cancer & Oncology Source Type: research

Correction to: CD163+CD14+ macrophages, a potential immune biomarker for malignant pleural effusion
(Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - August 4, 2021 Category: Cancer & Oncology Source Type: research

A comprehensive model based on temporal dynamics of peripheral T cell repertoire for predicting post-treatment distant metastasis of nasopharyngeal carcinoma
In conclusion, treatment had different effects on the composition of TCRB repertoire in patients without and with post-treat ment distant metastasis. The dynamics of TCRB diversity, the similarity of TCRB repertoires, and combinations of these factors with basic clinical characteristics could serve as noninvasive DMFS predictors for all NPC patients. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - August 3, 2021 Category: Cancer & Oncology Source Type: research

CD30+OX40+ Treg is associated with improved overall survival in colorectal cancer
AbstractRegulatory T cells (Tregs) are often enriched in tumors, where their immunosuppressive function has a key role in tumor persistence and progression. In colorectal cancer (CRC), however, Tregs are frequently associated with an improved clinical outcome. Tumor-infiltrating Tregs have been shown to exhibit a distinct signature comprising the co-stimulatory molecules (OX40, 4-1BB), cytokine receptors (IL1R2, IL21R, CCR8, CD30), and co-inhibitory molecules (PD-L1, TIGIT). Here, we showed by flow cytometry that circulating CD45RO+ Tregs from patients with CRC (n = 25) have elevated CD30 and OX40 expression ...
Source: Cancer Immunology, Immunotherapy - July 19, 2021 Category: Cancer & Oncology Source Type: research

Correction to: The predictive value of body mass index on prognosis and adverse events of cancers treated with immunotherapy: a systematic review and meta ‑analysis
A correction to this paper has been published: https://doi.org/10.1007/s00262-021-02907-6 (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - July 19, 2021 Category: Cancer & Oncology Source Type: research

Correction to: Mast cell proliferation in the cerebrospinal fluid after intraventricular administration of anti ‑B7H3 immunotherapy
A correction to this paper has been published: https://doi.org/10.1007/s00262-021-02942-3 (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - July 19, 2021 Category: Cancer & Oncology Source Type: research

Circulating regulatory T cells predict efficacy and atypical responses in lung cancer patients treated with PD-1/PD-L1 inhibitors
This study included 74 patients with advanced NSCLC who were treated with PD-1/PD-L1 inhibitors at Chungnam National University Hospital (CNUH) between January 2018 and August 2020. Chest X-rays were examined on day 7 after the first ICI dose to identify changes in the primary mass, and the response was assessed by computed tomography (CT). We evaluated circulating regulatory T (Treg) cells using flow cytometry and correlated the findings with clinical outcomes.ResultsThe incidence of pseudoprogression was 13.5%, and that of hyperprogression was 8.1%. On day 7 after initiation of treatment, the frequency of CD4+CD25+CD127l...
Source: Cancer Immunology, Immunotherapy - July 18, 2021 Category: Cancer & Oncology Source Type: research

Elevated expression of B7 homolog 4 is associated with disease progression in upper urinary tract urothelial carcinoma
ConclusionsThese findings suggest that B7-H4 expression in the tumor microenvironment influences the progression of UTUC through cancer immunity and metabolic activity. Tumor cell-associated B7-H4 might be a potential target for cancer immunotherapies. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - July 18, 2021 Category: Cancer & Oncology Source Type: research

Transcriptomic signatures of tumors undergoing T cell attack
ConclusionsThe TuTack scores measure the effects on tumor cells of an anti-tumor immune response and represent a comprehensive method to identify immunologically responsive tumors. Our findings suggest that TuTack may allow patient selection in immunotherapy clinical trials and warrant its application in multimodal biomarker strategies. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - July 17, 2021 Category: Cancer & Oncology Source Type: research

Identification of mouse helper epitopes for WT1-specific CD4+ T cells
This study describes the identification of three novel mouse Th epitope peptides, WT135-52, WT186-102 and WT1294-312, derived from WT1 protein, which is the most potent tumor-associated antigen. Compared to immunization with WT1 CTL peptide alone, immunization with the addition of these WT1-specific Th peptides strongly induced WT1-specific CTLs, continued to maintain them, and efficiently rejected the challenge of WT1-expressing tumor cells. Importantly, the majority of WT1-specific CTLs induced by the co-immunization with WT1 CTL and the WT1-specific Th peptides were CD44+CD62L− effector memory CD8+ T cells, which ...
Source: Cancer Immunology, Immunotherapy - July 16, 2021 Category: Cancer & Oncology Source Type: research

Radiotherapy planning parameters correlate with changes in the peripheral immune status of patients undergoing curative radiotherapy for localized prostate cancer
ConclusionsPatient age as well as radiotherapy planning parameters correlated with immune changes during radiotherapy. Larger irradiated volumes seem to correlate with early suppression of anti-cancer immunity. For immune cell analysis during normofractionated radiotherapy and correlations with treatment planning parameters, different time points should be looked at in future projects.Trial registration number:NCT01376674, 20.06.2011 (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - July 16, 2021 Category: Cancer & Oncology Source Type: research

A secondary role for hypoxia and HIF1 in the regulation of (IFN γ-induced) PD-L1 expression in melanoma
This study aims to explore the hypoxic regulation of PD-L1 expression in human melanoma, and its interaction with IFNγ-induced PD-L1 expression. Analysis of the cutaneous melanoma dataset from the cancer genome atlas revealed a significant correlation of the HIF1-signaling geneset signature withPD-L1 mRNA expression. However, this correlation is less pronounced than other key pathways known to control PD-L1 expression, including the IFN γ/JAK/STAT pathway. This secondary role of HIF1 in PD-L1 regulation was confirmed by analyzing single-cell RNA-sequencing data of 33 human melanoma tissues. Interestingly, PD-L1...
Source: Cancer Immunology, Immunotherapy - July 15, 2021 Category: Cancer & Oncology Source Type: research

Multiplexed single-cell pathology reveals the association of CD8 T-cell heterogeneity with prognostic outcomes in renal cell carcinoma
AbstractDespite the high sensitivity of renal cell carcinoma (RCC) to immunotherapy, RCC has been recognized as an unusual disease in which CD8+ T-cell infiltration into the tumor beds is related to a poor prognosis. To approach the inner landscape of immunobiology of RCC, we performed multiplexed seven-color immunohistochemistry (CD8, CD39, PD-1, Foxp3, PD-L1, and pan-cytokeratin AE1/AE3 with DAPI), which revealed the automated single-cell counts and calculations of individual cell-to-cell distances. In total, 186 subjects were included, in which CD39 was used as a marker for distinguishing tumor-specific (CD39+) and byst...
Source: Cancer Immunology, Immunotherapy - July 14, 2021 Category: Cancer & Oncology Source Type: research

Identification of KRAS G12V associated clonal neoantigens and immune microenvironment in long-term survival of pancreatic adenocarcinoma
ConclusionsThe genomic analysis of clonal neoantigens combined with tumor immune microenvironment could promote the understandings of personalized prognostic evaluation and the stratification of resected PAAD individuals with better outcome. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - July 13, 2021 Category: Cancer & Oncology Source Type: research

Modulation of CD47-SIRP α innate immune checkpoint axis with Fc-function detuned anti-CD47 therapeutic antibody
We report here the development and characterization of CC-90002, a humanized anti-CD47 antibody. CC-90002 is unique among previously reported anti-CD47 bivalent antibodies that it does not promote hemagglutination while maintaining high-affinity binding to CD47 and inhibition of the CD47–SIRPα interaction. Studies in a panel of hematological cancer cell lines showed concentration- dependent CC-90002-mediated phagocytosis in acute lymphoblastic leukemia, acute myeloid leukemia (AML), lenalidomide-resistant multiple myeloma (MM) cell lines and AML cells from patients. In vivo studies with MM cell line-derived xen...
Source: Cancer Immunology, Immunotherapy - July 10, 2021 Category: Cancer & Oncology Source Type: research

Anti-tumor effects of RTX-240: an engineered red blood cell expressing 4-1BB ligand and interleukin-15
AbstractRecombinant agonists that activate co-stimulatory and cytokine receptors have shown limited clinical anticancer utility, potentially due to narrow therapeutic windows, the need for coordinated activation of co-stimulatory and cytokine pathways and the failure of agonistic antibodies to recapitulate signaling by endogenous ligands. RTX-240 is a genetically engineered red blood cell expressing 4-1BBL and IL-15/IL-15R α fusion (IL-15TP). RTX-240 is designed to potently and simultaneously stimulate the 4-1BB and IL-15 pathways, thereby activating and expanding T cells and NK cells, while potentially offering an i...
Source: Cancer Immunology, Immunotherapy - July 9, 2021 Category: Cancer & Oncology Source Type: research

Intersection of Fc γRIIB, the microbiome, and checkpoint inhibitors in antitumor immunity
AbstractFc receptors (FcRs) and the microbiome are both known to have an effect on the development and progression of cancers. Checkpoint inhibitors are a novel class of therapeutics which are used to combat cancer and are integrally linked to both FcRs and the microbiome. The use of checkpoint inhibitors has grown exponentially over the past decade, although many host factors affect both the efficacy and the safety of these therapeutics. Some of these host factors, including the microbiome and the expression of FcRs, are currently being investigated. Here we discuss the current understanding of FcRs (particularly the inhi...
Source: Cancer Immunology, Immunotherapy - July 9, 2021 Category: Cancer & Oncology Source Type: research

Pre-pembrolizumab neutrophil-to-lymphocyte ratio (NLR) predicts the efficacy of second-line pembrolizumab treatment in urothelial cancer regardless of the pre-chemo NLR
AbstractNeutrophil-to-lymphocyte ratio (NLR) was reported to be associated with prognosis of urothelial cancer (UC) patients receiving systemic chemotherapy or immunotherapy. However, it has not been elucidated how preceding first-line chemotherapy affects NLR and subsequent second-line pembrolizumab treatment. This multicenter study analyzed 458 patients with metastatic UC who received first-line chemotherapy and second-line pembrolizumab with regard to pre-chemotherapy and pre-pembrolizumab NLR in association with the efficacy of chemotherapy and pembrolizumab treatment. NLR was increased in 47% while decreased in 53% of...
Source: Cancer Immunology, Immunotherapy - July 7, 2021 Category: Cancer & Oncology Source Type: research

Correction to: Metabolic reprogramming of T regulatory cells in the hypoxic tumor microenvironment
(Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - July 7, 2021 Category: Cancer & Oncology Source Type: research

Small cell lung cancer stem cells display mesenchymal properties and exploit immune checkpoint pathways in activated cytotoxic T lymphocytes
In conclusion, our data provide evidence for the superio r potential of the SCLC cells with stem-like and mesenchymal properties to gain immune regulatory capacities and cope with cytotoxic T cell responses. With their high metastatic and immune-modulatory assets, the CSC subpopulation in SCLC may serve as a preferential target for checkpoint blockade imm unotherapy . (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - July 6, 2021 Category: Cancer & Oncology Source Type: research

Epigenetic therapy in combination with a multi-epitope cancer vaccine targeting shared tumor antigens for high-risk myelodysplastic syndrome  - a phase I clinical trial
ConclusionThe patients progressed to AML with an average time of only five months after initiating the combination therapy. This may be unrelated to the experimental treatment, but the trial was terminated early as there was no sign of clinical benefit or immunological response.Why the manuscript is especially interestingThis study is the first to exploit the potential synergistic effects of combining a multi-peptide cancer vaccine with epigenetic therapy in MDS. Although our results are negative, they emphasize challenges to induce immune reactivity in patients with high-risk MDS. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - July 4, 2021 Category: Cancer & Oncology Source Type: research

Stem cells-derived natural killer cells for cancer immunotherapy: current protocols, feasibility, and benefits of ex vivo generated natural killer cells in treatment of advanced solid tumors
AbstractNowadays, natural killer (NK) cell-based immunotherapy provides a practical therapeutic strategy for patients with advanced solid tumors (STs). This approach is adaptively conducted by the autologous and identical NK cells after in vitro expansion and overnight activation. However, the NK cell-based cancer immunotherapy has been faced with some fundamental and technical limitations. Moreover, the desirable outcomes of the NK cell therapy may not be achieved due to the complex tumor microenvironment by inhibition of intra-tumoral polarization and cytotoxicity of implanted NK cells. Currently, stem cells (SCs) techno...
Source: Cancer Immunology, Immunotherapy - July 4, 2021 Category: Cancer & Oncology Source Type: research

First-in-human phase 1 study of budigalimab, an anti-PD-1 inhibitor, in patients with non-small cell lung cancer and head and neck squamous cell carcinoma
ConclusionsThe safety, efficacy and biomarker profiles of budigalimab are similar to other PD-1 inhibitors. Development of budigalimab in combination with novel anticancer agents is ongoing. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - July 3, 2021 Category: Cancer & Oncology Source Type: research

T cells, particularly activated CD4+ cells, maintain anti-CD20-mediated NK cell viability and antibody dependent cellular cytotoxicity
AbstractAnti-CD20 monoclonal antibody (mAb) therapy is a mainstay of therapy for B cell malignancies, however many patients fail to respond or eventually develop resistance. The current understanding of mechanisms responsible for this resistance is limited. When peripheral blood mononuclear cells of healthy donors were cultured with Raji cells for 7  days, rituximab (RTX) induced NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC), enhanced NK cell viability and increased or maintained NK expression of CD56, CD16, CD57 and KIR. T cells, mainly CD4+, mediated these changes in a contact-dependent manner, wi...
Source: Cancer Immunology, Immunotherapy - June 10, 2021 Category: Cancer & Oncology Source Type: research

Clinical benefit of continuing pembrolizumab treatment beyond progression in patients with metastatic urothelial carcinoma
ConclusionsContinued pembrolizumab administration beyond progression might be beneficial in patients with metastatic UC who were clinically stable. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - June 8, 2021 Category: Cancer & Oncology Source Type: research

ICI plus chemotherapy prolonged survival over ICI alone in patients with previously treated advanced NSCLC
This study aims to investigate the efficacy of ICI plus chemotherapy in patients with previously treated advanced NSCLC.Patients and methodsAn investigator-initiated trial (IIT) aiming to evaluate the efficacy and safety of ICI in combination with chemotherapy as second line and beyond for patients with advanced NSCLC was undergone at Shanghai Pulmonary Hospital (ChiCTR1900026203). Patients who received ICI monotherapy as second or later line setting during the same period were also collected as a comparator.ResultsFrom April 2018 to June 2019, 31 patients were included into this IIT study, simultaneously 51 patients treat...
Source: Cancer Immunology, Immunotherapy - June 7, 2021 Category: Cancer & Oncology Source Type: research

Increased serum cholesterol and long-chain fatty acid levels are associated with the efficacy of nivolumab in patients with non-small cell lung cancer
AbstractBackgroundLipids have immunomodulatory functions and the potential to affect cancer immunity.MethodsThe associations of pretreatment serum cholesterol and long-chain fatty acids with the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were evaluated in 148 patients with non-small cell lung cancer who received nivolumab.ResultsWhen each lipid was separately evaluated, increased low-density lipoprotein (LDL)-cholesterol (P
Source: Cancer Immunology, Immunotherapy - June 5, 2021 Category: Cancer & Oncology Source Type: research

Maintenance of WT1 expression in tumor cells is associated with a good prognosis in malignant glioma patients treated with WT1 peptide vaccine immunotherapy
This study provides insight into the mechanisms of intra-tumoral immune reaction/escape during WT1 peptide vaccine treatment and suggests potential clinical strategies for cancer immunotherapy. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - June 5, 2021 Category: Cancer & Oncology Source Type: research

Correction to: Tumour draining lymph node-generated CD8 T cells play a role in controlling lung metastases after a primary tumour is removed but not when adjuvant immunotherapy is used
A correction to this paper has been published: https://doi.org/10.1007/s00262-021-02970-z (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - June 5, 2021 Category: Cancer & Oncology Source Type: research

STAT3 is over-activated within CD163pos bone marrow macrophages in both Multiple Myeloma and the benign pre-condition MGUS
In conclusion, macrophage-related inflammatory changes, including activation of STAT3, were present already at the MGUS stage, at similar levels as in MM. Specific increase in pSTAT3 levels within CD163pos cells supports that the CD163 scavenger receptor may be a useful target for future delivery of STAT3-inhibitory drugs to TAMs in MM patients. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - June 1, 2021 Category: Cancer & Oncology Source Type: research

Blood serum amyloid A as potential biomarker of pembrolizumab efficacy for patients affected by advanced non-small cell lung cancer overexpressing PD-L1: results of the exploratory “FoRECATT” study
AbstractBackgroundIdentifying the patients who may benefit the most from immune checkpoints inhibitors remains a great challenge for clinicians. Here we investigate on blood serum amyloid A (SAA) as biomarker of response to upfront pembrolizumab in patients with advanced non-small-cell lung cancer (NSCLC).MethodsPatients with PD-L1  ≥ 50% receiving upfront pembrolizumab (P cohort) and with PD-L1 0–49% treated with chemotherapy (CT cohort) were evaluated for blood SAA and radiological response at baseline and every 9 weeks. Endpoints were response rate (RR) according to RECIST1.1, progression-fre...
Source: Cancer Immunology, Immunotherapy - May 22, 2021 Category: Cancer & Oncology Source Type: research