Expansions of tumor-reactive Vdelta1 gamma-delta T cells in newly diagnosed patients with chronic myeloid leukemia
AbstractRecent studies have underscored the importance of gamma-delta ( γδ) T cells in mediating potent MHC-unrestricted cytotoxicity in numerous malignancies. Here, we analyzed Vδ1 and Vδ2 γδ T cell subsets in newly diagnosed chronic myeloid leukemia (CML) patients (n = 40) who had initiated tyrosine kinase inhibitor (TKI) therapy including imatinib (n = 22), nilotinib (n = 14) and dasatinib (n = 4). Patient peripheral blood samples were analyzed at diagnosis and monitored prospectively at 3, 6, 12 and 18 months post-TKI. γδ T cells isolated from healthy donors and CML patients were used against K...
Source: Cancer Immunology, Immunotherapy - April 18, 2023 Category: Cancer & Oncology Source Type: research
Somatic ARID1A mutation stratifies patients with gastric cancer to PD-1 blockade and adjuvant chemotherapy
ConclusionsARID1A-mutant GC displayed immunogenic TME and might be a candidate for both monotherapy and the combination of frontline chemotherapy and PD-1 blockade. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - April 18, 2023 Category: Cancer & Oncology Source Type: research
Novel ocular immunotherapy induces tumor regression in an equine model of ocular surface squamous neoplasia
AbstractOcular surface squamous neoplasia (OSSN) is the major cause of corneal cancer in man and horses worldwide, and the prevalence of OSSN is increasing due to greater UVB exposure globally. Currently, there are no approved treatments for OSSN in either species, and most patients are managed with surgical excision or off-label treatment with locally injected interferon alpha, or topically applied cytotoxic drugs such as mitomycin C. A more broadly effective and readily applied immunotherapy could exert a significant impact on management of OSSN worldwide. We therefore evaluated the effectiveness of a liposomal TLR compl...
Source: Cancer Immunology, Immunotherapy - April 18, 2023 Category: Cancer & Oncology Source Type: research
Egr2 and 3 maintain anti-tumour responses of exhausted tumour infiltrating CD8 + T cells
AbstractAlthough T cells can develop into an exhausted state in the tumour microenvironment, tumour infiltrating T cells (TILs) are important to control tumour growth. By analysing single cell RNA-sequencing data from human tumours, we found that the transcription factors Early Growth Response 2 (EGR2) and 3 were highly induced in TILs, but not peripheral CD8 + T cells, in multiple patient cohorts. We found that deficiency of Egr2 and 3 in T cells resulted in enhanced tumour growth and fewer TILs in mouse models. Egr2 is highly expressed together with checkpoint molecules in a proportion of CD8 + TILs and Egr2high...
Source: Cancer Immunology, Immunotherapy - April 18, 2023 Category: Cancer & Oncology Source Type: research
Pre-treatment soluble PD-L1 as a predictor of overall survival for immune checkpoint inhibitor therapy: a systematic review and meta-analysis
ConclusionsWe found significantly inferior OS in ICI-treated cancer patients with elevated pre-treatment sPD-L1 levels, but this association seems to be tumor type dependent. In addition, sPD-L1 increases during anti-PD-L1 therapy seems to be therapy specific. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - April 18, 2023 Category: Cancer & Oncology Source Type: research
Expansion of KRAS hotspot mutations reactive T cells from human pancreatic tumors using autologous T cells as the antigen-presenting cells
AbstractAdoptive cell therapy (ACT) with expanded tumor-infiltrating lymphocytes (TIL) or TCR gene-modified T cells (TCR-T) that recognize mutant KRAS neo-antigens can mediate tumor regression in patients with advanced pancreatic ductal adenocarcinoma (PDAC) (Tran et al in N Engl J Med, 375:2255 –2262, 2016; Leidner et al in N Engl J Med, 386:2112–2119, 2022). The mutant KRAS-targeted ACT holds great potential to achieve durable clinical responses for PDAC, which has had no meaningful improvement over 40 years. However, the wide application of mutant KRAS-centric ACT is currently limit ed by the rarity of TIL that rec...
Source: Cancer Immunology, Immunotherapy - April 18, 2023 Category: Cancer & Oncology Source Type: research
Transcriptomic characterization and construction of M2 macrophage-related prognostic and immunotherapeutic signature in ovarian metastasis of gastric cancer
ConclusionTranscriptomic characterization of paired normal mucosae, primary and ovarian metastatic tumors revealed their unique molecular and immune features. Follow-up analyses established a novel OM- and M2 macrophage-related signature, M2GO, which served as a promising prognostic and immunotherapeutic biomarker to distinguish the clinical outcome, molecular and immune features of GC patients and predict their differential responses to immunotherapy. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - April 18, 2023 Category: Cancer & Oncology Source Type: research
Identification of TCR rearrangements specific for genetic alterations in EGFR-mutated non-small cell lung cancer: results from the ADJUVANT-CTONG1104 trial
In this study, tumor tissues were collected from 101 patients with stage II/III resectable NSCLC with anEGFR mutation (57 patients were treated with gefitinib and 44 were treated with chemotherapy) in the ADJUVANT-CTONG1104 trial for high-throughput TCR β V region and exome sequencing. Ten clonal TCRs were associated withEGFR exon 19 deletion (del),EGFR exon 21 mutation (L858R),RB1 alteration,TP53 exon 4/5 missense mutation,TP53 nonsense mutation, or copy number gains inNKX2-1 andCDK4. Among the TCRs, there was frequent use of V β20-1Jβ2-3 specifically forEGFR exon 19 del or V β9Jβ2-1 specifically forEGFR exon 21 muta...
Source: Cancer Immunology, Immunotherapy - April 18, 2023 Category: Cancer & Oncology Source Type: research
Local immunotherapy with the RNA-based immune stimulator CV8102 induces substantial anti-tumor responses and enhances checkpoint inhibitor activity
AbstractImmunotherapy has revolutionized cancer treatment in recent years. Although currently approved checkpoint inhibitors (CPIs) yield remarkable anti-tumoral responses in several cancer types, a substantial proportion of patients do not benefit from such therapies. Local activation of innate immune signaling pathways is a promising approach to overcome the immunosuppressive tumor microenvironment, induce anti-tumor immunity, and improve the efficacy of CPI therapies. Here, we assessed the mode of action and efficacy of the RNA-based innate immune stimulator CV8102 for local immunotherapy in preclinical models. Intratum...
Source: Cancer Immunology, Immunotherapy - April 18, 2023 Category: Cancer & Oncology Source Type: research
Senescence-associated secretory proteins induced in lung adenocarcinoma by extended treatment with dexamethasone enhance migration and activation of lymphocytes
AbstractThere is a need to improve response rates of immunotherapies in lung adenocarcinoma (AC). Extended (7 –14 days) treatment of high glucocorticoid receptor (GR) expressing lung AC cells with dexamethasone (Dex) induces an irreversible senescence phenotype through chronic induction of p27. As the senescence-associated secretory phenotype (SASP) may have either tumor supporting or antitumor immunomod ulatory effects, it was interest to examine the effects of Dex-induced senescence of lung AC cells on immune cells. Dex-induced senescence resulted in sustained production of CCL2, CCL4, CXCL1 and CXCL2, both in vitro a...
Source: Cancer Immunology, Immunotherapy - April 18, 2023 Category: Cancer & Oncology Source Type: research
Nonlinear association between body mass index and overall survival in advanced NSCLC patients treated with immune checkpoint blockade
ConclusionWe observed a nonlinear association between BMI and OS following treatment with ICI in advanced NSCLC. Risk of death increases at both extremes of BMI with a nadir that exists around 30 kg/m2. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - April 18, 2023 Category: Cancer & Oncology Source Type: research
Combined pembrolizumab and bevacizumab therapy effectively inhibits non-small-cell lung cancer growth and prevents postoperative recurrence and metastasis in humanized mouse model
In this study, we hypothesized that combining immunotherapy with anti-angiogenic therapy may have a synergistic effect in local tumor control and neoadjuvant therapy. To this end, the effect of combination of bevacizumab and pembrolizumab in humanized mouse models was evaluated. Furthermore, we innovatively constructed a neoadjuvant mouse model that can simulate postoperative recurrence and metastasis of NSCLC to perform neoadjuvant study. Tumor growth and changes in the tumor vasculature, along with the frequency and phenotype of tumor-infiltrating lymphocytes, were examined. Additionally, in vivo imaging system (IVIS) wa...
Source: Cancer Immunology, Immunotherapy - April 18, 2023 Category: Cancer & Oncology Source Type: research
Inhibition of the CCR6-CCL20 axis prevents regulatory T cell recruitment and sensitizes head and neck squamous cell carcinoma to radiation therapy
Conclusion Our results suggest that radiation promotes CCL20 secretion by tumor cells which is responsible for the attraction of Tregs. Inhibition of the CCR6-CCL20 axis prevents infiltration of Tregs in tumors and suppresses tumor growth resulting in improved response to radiation. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - April 18, 2023 Category: Cancer & Oncology Source Type: research
Safety and efficacy of the anti-PD1 immunotherapy with nivolumab in trichoblastic carcinomas
AbstractTrichoblastic carcinoma is a rare malignant cutaneous adnexal tumor with a risk of local invasion and distant metastasis. As of today, there is no consensus for the treatment of locally advanced or metastatic trichoblastic carcinoma. “AcSé Nivolumab” is a multi-center Phase II basket clinical trial (NCT03012581) evaluating the safety and efficacy of nivolumab in several cohorts of rare, advanced cancers. Here we report the results of nivolumab in patients with trichoblastic carcinoma. Of the eleven patients enrolled in the study, five patients had been previously treated by sonic hedgehog inhibitors. The prima...
Source: Cancer Immunology, Immunotherapy - April 17, 2023 Category: Cancer & Oncology Source Type: research
Correction to: LILRB2-containing small extracellular vesicles from glioblastoma promote tumor progression by promoting the formation and expansion of myeloid-derived suppressor cells
(Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - April 17, 2023 Category: Cancer & Oncology Source Type: research
