Inflammasome activation, NLRP3 engagement and macrophage recruitment to tumor microenvironment are all required for Salmonella antitumor effect
AbstractSalmonella-based cancer therapies show great potential in preclinical models, but for most cases the observed antitumor effect is transient. Understanding the basis of the antitumor efficacy might guide the design of improved strains that elicit long-lasting effects, paving the wave for clinical use.  Here, we deepened into the role of macrophages and inflammasome activation in the context ofSalmonella anti-melanoma effect. We showed inflammasome activation in melanoma cells upon infection, which correlated with cell surface exposure of gasdermin-D (GSDM-D) and calreticulin (CRT) and High mobility group box 1 ...
Source: Cancer Immunology, Immunotherapy - January 21, 2022 Category: Cancer & Oncology Source Type: research

Naringenin potentiates anti-tumor immunity against oral cancer by inducing lymph node CD169-positive macrophage activation and cytotoxic T cell infiltration
AbstractThe CD169+ macrophages in lymph nodes are implicated in cytotoxic T lymphocyte (CTL) activation and are associated with improved prognosis in several malignancies. Here, we investigated the significance of CD169+ macrophages in oral squamous cell carcinoma (OSCC). Further, we tested the anti-tumor effects of naringenin, which has been previously shown to activate CD169+ macrophages, in a murine OSCC model. Immunohistochemical analysis for CD169 and CD8 was performed on lymph node and primary tumor specimens from 89 patients with OSCC. We also evaluated the effects of naringenin on two murine OSCC models. Increased ...
Source: Cancer Immunology, Immunotherapy - January 19, 2022 Category: Cancer & Oncology Source Type: research

Prognostic value, DNA variation and immunologic features of a tertiary lymphoid structure-related chemokine signature in clear cell renal cell carcinoma
ConclusionThis study described a 12-chemokine gene signature for TLS in ccRCC and established TLS clusters that reflected different TME immune status and corresponded to prognosis of ccRCC. We confirmed the dense presence of TILs aggregation and TLS in ccRCC and demonstrated an oncogenic role ofCXCL13 expression of ccRCC, which help develop immunotherapies and provide novel insights on the long-term management of ccRCC. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - January 19, 2022 Category: Cancer & Oncology Source Type: research

Immune inactivation by neuropilin-1 predicts clinical outcome and therapeutic benefit in muscle-invasive bladder cancer
ConclusionsOur study firstly identified and validated the clinical implications of NRP1 expression for prognosis and systematic therapeutic responses (PD-L1 blockade and ACT) in MIBC. NRP1 expression was associated with an immunosuppressive microenvironment with dysfunctional effector immune cells. Prospective investigations of its roles in the therapeutic landscape of MIBC warrant more consideration. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - January 18, 2022 Category: Cancer & Oncology Source Type: research

Novel inhibitor of hematopoietic cell kinase as a potential therapeutic agent for acute myeloid leukemia
In conclusion, the iHCK-37 inhibitor has anti-neoplastic activity in leukemia cells without altering apoptosis and survival rate of normal cells, suggesting on-target malignant cell killing activity as a single agent or in combination with 5-Azacytidine or Cytarabine. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - January 18, 2022 Category: Cancer & Oncology Source Type: research

Cancer bio-immunotherapy XVIII annual NIBIT-(Italian network for tumor biotherapy) meeting, October 15 –16, 2020
(Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - January 16, 2022 Category: Cancer & Oncology Source Type: research

Pancreatic cancer survival prediction via inflammatory serum markers
AbstractBackgroundFor prognostic evaluation of pancreatic ductal adenocarcinoma (PDAC), the only well-established serum marker is carbohydrate antigen CA19-9. To improve the accuracy of survival prediction, we tested the efficacy of inflammatory serum markers.MethodsA preoperative serum panel comprising 48 cytokines plus high-sensitivity CRP (hs-CRP) was analyzed in 173 stage I –III PDAC patients. Analysis of the effect of serum markers on survival utilized the Cox regression model, with the most promising cytokines chosen with the aid of the lasso method. We formed a reference model comprising age, gender, tumor sta...
Source: Cancer Immunology, Immunotherapy - January 16, 2022 Category: Cancer & Oncology Source Type: research

Pre-treatment serum protein levels predict survival of non-small cell lung cancer patients without durable clinical benefit by PD-1/L1 inhibitors
In conclusion, serum levels of CRP and follistatin before ICI initiation, not at the time of PD, are predictive for OS in NDBs, suggesting long-term survivor in NDBs are predetermined by the immune status before ICI initiation. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - January 16, 2022 Category: Cancer & Oncology Source Type: research

Antibody-dependent cellular phagocytosis of tropomyosin receptor kinase C (TrkC) expressing cancer cells for targeted immunotherapy
This study illustrates how hapten-based pre-immunization (for anti-hapten antibodies production) combi ned with cancer receptor labeling with hapten antigen constructs can elicit antibody-dependent cellular phagocytosis (ADCP). Thus, the hapten antigen 2,4-dinitrophenol (DNP) was covalently combined with a cancer receptor-binding dipeptide (IYIY) to form a dipeptide-hapten construct (IYIY-DNP, MW =  1322.33) that targets the tropomyosin receptor kinase C (TrkC)-expressed on the surface of metastatic cancer cells. IYIY-DNP facilitated selective association of RAW264.7 macrophages to the TrkC expressing 4T1 can...
Source: Cancer Immunology, Immunotherapy - January 15, 2022 Category: Cancer & Oncology Source Type: research

A real-world study of the efficacy and safety of anti-PD-1 antibodies plus lenvatinib in patients with advanced gallbladder cancer
ConclusionAnti-PD-1 antibodies plus lenvatinib represent an effective and tolerable therapy for patients with advanced gallbladder cancer. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - January 13, 2022 Category: Cancer & Oncology Source Type: research

Associations between immune-related thyroid dysfunction and efficacy of immune checkpoint inhibitors: a systematic review and meta-analysis
AbstractBackgroundThere is growing evidence suggesting that the occurrence of immune-related adverse events (irAEs) may be a predictor of immune checkpoint inhibitor efficacy. Whether this association extends to all irAEs or just those within particular organs/systems is yet to be resolved. As immune-related thyroid dysfunction (thyroid irAE) is one of the most commonly reported irAEs, this study aims to summarize the available data and determine if thyroid irAE is a surrogate marker for improved cancer outcomes during ICI therapy.MethodsPubMed, EMBASE and Cochrane Library were searched up to July 1st 2021 for studies asse...
Source: Cancer Immunology, Immunotherapy - January 13, 2022 Category: Cancer & Oncology Source Type: research

Interleukin-12 as an in situ cancer vaccine component: a review
We describe different methods of IL-12 delivery, both systemic and local, and ultimately highlight the potential of an in situ vaccination approach for minimizing toxicities and providing antitumor efficacy. This review offers a basis for pursuing an in situ vaccine approach that may eventually allow IL-12 to be more readily integrated as an immunotherapy into the clinical treatment of cancers. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - January 13, 2022 Category: Cancer & Oncology Source Type: research

Pediatric glioblastoma: mechanisms of immune evasion and potential therapeutic opportunities
AbstractPediatric glioblastoma is relatively rare compared with its adult counterpart but is associated with a similarly grim prognosis. Available data indicate that pediatric glioblastomas are molecularly distinct from adult tumors, and relatively little is known about the pediatric glioblastoma tumor microenvironment (TME). Cancer immunotherapy has emerged as a new pillar of cancer treatment and is revolutionizing the care of patients with many advanced solid tumors, including melanoma, non-small cell lung cancer, head and neck cancer, and renal cell carcinoma. Unfortunately, attempts to treat adult glioblastoma with cur...
Source: Cancer Immunology, Immunotherapy - January 12, 2022 Category: Cancer & Oncology Source Type: research

Vaccination against galectin-1 promotes cytotoxic T-cell infiltration in melanoma and reduces tumor burden
AbstractGalectin-1 (Gal1) is a glycan-binding protein that promotes tumor progression by several distinct mechanisms. Through direct binding to vascular endothelial growth factor (VEGF)-receptor 2, Gal1 is able to induce VEGF-like signaling, which contributes to tumor angiogenesis. Furthermore, several studies have demonstrated an immunosuppressive function of Gal1 through effects on both effector and regulatory T cells. Elevated Gal1 expression and secretion have been shown in many tumor types, and high Gal1 serum levels have been connected to poor prognosis in cancer patients. These findings suggest that therapeutic stra...
Source: Cancer Immunology, Immunotherapy - January 11, 2022 Category: Cancer & Oncology Source Type: research

Selection of antibody and light exposure regimens alters therapeutic effects of EGFR-targeted near-infrared photoimmunotherapy
In this study, we compared panitumumab and cetuximab in APCs for NIR-PIT, and single and double light exposures using a newly established hEGFR-expressing cancer cell line derived from immunocompetent C57BL/6 mice (mEERL-hEGFR cell line). Fluorescence imaging showed that the decline of pan-IR700 was slower than cet-IR700 confirming a longer clearance time. Among all the combinations tested, mice receiving pan-IR700 and double light exposure showed the greatest tumor growth inhibition. This group was also shown to activate CD8+ T lymphocytes in lymph nodes and accumulate CD8+ T lymphocytes to a greater extent within the tum...
Source: Cancer Immunology, Immunotherapy - January 11, 2022 Category: Cancer & Oncology Source Type: research

Functional virus-specific memory T cells survey glioblastoma
AbstractGlioblastoma multiforme (GBM) is among the most aggressive, treatment-resistant cancers, and despite standard of care surgery, radiation and chemotherapy, is invariably fatal. GBM is marked by local and systemic immunosuppression, contributing to resistance to existing immunotherapies that have had success in other tumor types. Memory T cells specific for previous infections reside in tissues throughout the host and are capable of rapid and potent immune activation. Here, we show that virus-specific memory CD8  + T cells expressing tissue-resident markers populate the mouse and human glioblastoma micr...
Source: Cancer Immunology, Immunotherapy - January 10, 2022 Category: Cancer & Oncology Source Type: research

Hypoxia-inducible factor-1 alpha expression is induced by IL-2 via the PI3K/mTOR pathway in hypoxic NK cells and supports effector functions in NKL cells and ex vivo expanded NK cells
AbstractNatural killer (NK) cells are cytotoxic innate lymphocytes that are specialized to kill tumor cells. NK cells are responsive to the primary cytokine IL-2 in the tumor microenvironment (TME), to activate its effector functions against tumors. Despite their inherent ability to kill tumor cells, dysfunctional NK cells observed within advanced solid tumors are associated with poor patient survival. Hypoxia in the TME is a major contributor to immune evasion in solid tumors that could contribute to impaired NK cell function. HIF-1 α is a nodal regulator of hypoxia in driving the adaptive cellular responses to chan...
Source: Cancer Immunology, Immunotherapy - January 9, 2022 Category: Cancer & Oncology Source Type: research

Combination immunotherapy including OncoVEXmGMCSF creates a favorable tumor immune micro-environment in transgenic BRAF murine melanoma
This study provides rational basis to combine targeted agents, oncolytic viral therapy, and checkpoint inhibitors in the treatment of melanoma. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - January 9, 2022 Category: Cancer & Oncology Source Type: research

Combined treatment with anti-HER2/neu and anti-4-1BB monoclonal antibodies induces a synergistic antitumor effect but requires dose optimization to maintain immune memory for protection from lethal rechallenge
AbstractHuman epidermal growth factor receptor type 2 (HER2)-positive breast cancer that is treated with anti-HER2/neu monoclonal antibody (mAb) is not free from late recurrences. Addition of anti-4-1BB mAb to anti-HER2/neu mAb has been demonstrated to strengthen the cytotoxic antitumor response. Our study expands on this by revealing the influence of anti-4-1BB mAb addition on the immune memory of anti-HER2/neu mAb. We designed murine breast cancer models by implanting TUBO and TUBO-P2J cell lines in mice, which were then treated with anti-HER2/neu and/or anti-4-1BB mAb. After complete surgical and/or chemical regression ...
Source: Cancer Immunology, Immunotherapy - January 6, 2022 Category: Cancer & Oncology Source Type: research

The integration of systemic and tumor PD-L1 as a predictive biomarker of clinical outcomes in patients with advanced NSCLC treated with PD-(L)1blockade agents
ConclusionsOur results suggest that integrating circulating PD-L1  + leukocytes, PLT, PMPs, and sPD-L1 and tumor PD-L1 expression may be helpful to decide on the best treatment strategy in patients with advanced NSCLC who are candidates for PD-(L)1 blockade agents. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - January 5, 2022 Category: Cancer & Oncology Source Type: research

Safety, antitumor activity and biomarkers of sugemalimab in Chinese patients with advanced solid tumors or lymphomas: results from the first-in-human phase 1 trial
ConclusionsSugemalimab was well-tolerated and showed promising antitumor activity as monotherapy or in combination with SOC chemotherapy in advanced malignancies.This trial was registered with ClinicalTrials.gov on Oct 18, 2017, number NCT03312842. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - January 5, 2022 Category: Cancer & Oncology Source Type: research

A phase I dose-escalation, safety/tolerability, and preliminary efficacy study of the intratumoral administration of GEN0101 in patients with advanced melanoma
AbstractDespite recent advance in immunotherapy agents, safe new therapies that enhance the effects of immune checkpoint inhibitors are still required to develop. We previously demonstrated that hemagglutinating virus of Japan-envelope (HVJ-E) induced not only direct tumor cell death but also antitumor immunity through the activation of T and natural killer (NK) cells, thereafter, developed a manufacturing process of HVJ-E (GEN0101) for clinical use. We here performed a phase Ia clinical trial of intratumoral GEN0101 administration in six patients with stage IIIC or IV malignant melanoma. The primary aim was to evaluate th...
Source: Cancer Immunology, Immunotherapy - January 5, 2022 Category: Cancer & Oncology Source Type: research

Oral administration of a whole glucan particle (WGP)-based therapeutic cancer vaccine targeting macrophages inhibits tumor growth
AbstractAlthough therapeutic cancer vaccines have been gaining substantial ground, the development of cancer vaccines is impeded because of the undegradability of delivery systems, ineffective delivery of tumor antigens and weak immunogenicity of adjuvants. Here, we made use of a whole glucan particle (WGP) to encapsulate ovalbumin (OVA), thereby formulating a novel cancer vaccine. Results from in vitro experiments showed that WGP-OVA not only induced the activation of bone marrow-derived macrophages (BMDMs) including driving M0 BMDM polarization to the M1 phenotype, upregulating the costimulatory molecules and inducing th...
Source: Cancer Immunology, Immunotherapy - January 4, 2022 Category: Cancer & Oncology Source Type: research

Construction of TME and Identification of crosstalk between malignant cells and macrophages by SPP1 in hepatocellular carcinoma
In this study, we investigated the immune microenvironment by multiomics analysis. The tumour immune infiltration characteristics of HCC were determined at the genomic, epigenetic, bulk transcriptome and single-cell levels by data from The Cancer Genome Atlas portal and the Gene Expression Omnibus (GEO). An epigenetic immune-related scoring system (EIRS) was developed to stratify patients with poor prognosis. SPP1, one gene in the EIRS system, was identified as an immune-related predictor of poor survival in HCC patients. Through receptor-ligand pair analysis in single-cell RNA-seq, SPP1 was indicated to mediate the crosst...
Source: Cancer Immunology, Immunotherapy - January 1, 2022 Category: Cancer & Oncology Source Type: research

Impact of preoperative plasma levels of interleukin 6 and interleukin 6 soluble receptor on disease outcomes after radical cystectomy for bladder cancer
AbstractBackgroundPreoperative plasma levels of Interleukin 6 (IL6) and its soluble receptor (IL6sR) have previously been associated with oncologic outcomes in urothelial carcinoma of the bladder (UCB); however, external validation in patients treated with radical cystectomy (RC) for UCB is missing.Patients/methodsWe prospectively collected preoperative plasma from 1,036 consecutive patients at two institutes. These plasma specimens were assessed for levels of IL6 and IL6sR. Logistic and Cox regression analyses were used to assess the correlation of plasma levels with pathologic and survival outcomes. The additional clinic...
Source: Cancer Immunology, Immunotherapy - January 1, 2022 Category: Cancer & Oncology Source Type: research

CD74+ macrophages are associated with favorable prognosis and immune contexture in hepatocellular carcinoma
In this study, HCC tissues from Zhongshan Hospital and data from The Cancer Genome Atlas (TCGA) were obtained and analyzed. Immunohistochemistry, flow cytometry, and single-cell RNA sequencing (scRNA-seq) were performed to detect the characteristics of CD74+ cells and explore their impact on the tumor microenvironment (TME) of HCC. Our data revealed that stromal CD74+ cell enrichment was associated with favorable prognosis in patients with HCC. CD74 was abundant in a large portion of HCC specimens and prominently distributed on stromal macrophages. scRNA-seq data also indicated that the pathways related to immune response ...
Source: Cancer Immunology, Immunotherapy - January 1, 2022 Category: Cancer & Oncology Source Type: research

Intratumoral Foxp3+ROR γt+ T cell infiltration determines poor prognosis and immunoevasive contexture in gastric cancer patients
ConclusionsWe found that Foxp3+RORγt+ T cells could potentially attenuate effective functions of CD8+ T cells and led to adverse survival outcomes and inferior chemotherapeutic responsiveness. Moreover, the novel co-evaluation system might be useful for prognosis prediction for appropriate treatment in gastric cancer.Novelty and impact statementsClinical significance of Foxp3+RORγts+ T cells has not been studied in gastric cancer. Herein, we investigated the prognostic value of Foxp3+RORγt+ T cells in 452 patients. We demonstrated that intratumoral Foxp3+RORγt+ T cell infiltration was a prognostic b...
Source: Cancer Immunology, Immunotherapy - January 1, 2022 Category: Cancer & Oncology Source Type: research

Engineering a natural ligand-based CAR: directed evolution of the stress-receptor NKp30
AbstractB7H6, a stress-induced ligand which binds to the NK cell receptor NKp30, has recently emerged as a promising candidate for immunotherapy due to its tumor-specific expression on a broad array of human tumors. NKp30 can function as a chimeric antigen receptor (CAR) extracellular domain but exhibits weak binding with a fast on and off rate to B7H6 compared to the TZ47 anti-B7H6 single-chain variable fragment (scFv). Here, directed evolution using yeast display was employed to isolate novel NKp30 variants that bind to B7H6 with higher affinity compared to the native receptor but retain its fast association and dissocia...
Source: Cancer Immunology, Immunotherapy - January 1, 2022 Category: Cancer & Oncology Source Type: research

CD40 and CD80/86 signaling in cDC1s mediate effective neoantigen vaccination and generation of antigen-specific CX3CR1+ CD8+ T cells
AbstractThe use of tumor mutation-derived neoantigen represents a promising approach for cancer vaccines. Preclinical and early phase human clinical studies have shown the successful induction of tumor neoepitope-directed responses; however, overall clinical efficacy of neoantigen vaccines has been limited. One major obstacle of this strategy is the prevailing lack of sufficient understanding of the mechanism underlying the generation of neoantigen-specific CD8+ T cells. Here, we report a correlation between antitumor efficacy of neoantigen/toll-like receptor 3 (TLR3)/CD40 agonists vaccination and an increased frequency of...
Source: Cancer Immunology, Immunotherapy - January 1, 2022 Category: Cancer & Oncology Source Type: research

PTCH1 mutation promotes antitumor immunity and the response to immune checkpoint inhibitors in colorectal cancer patients
AbstractImmunotherapy has emerged as an effective therapeutic strategy for various cancers, including colorectal cancer (CRC), but only a subset of MSI-H patients can benefit from such therapy. Patched1 (PTCH1) is a frequently altered gene in CRCs and its mutations contribute to unregulated Hedgehog (Hh) signaling. In the study, we evaluated the association ofPTCH1 mutations with CRC immunity based on our single-center cohort and multiple cancer genomic datasets. Among 21 enrolled patients, six (28.6%) harbored aPTCH1 mutation based on WES analyses. In CRC patients, thePTCH1 mutation subgroup experienced a higher durable c...
Source: Cancer Immunology, Immunotherapy - January 1, 2022 Category: Cancer & Oncology Source Type: research

SIRP α-specific monoclonal antibody enables antibody-dependent phagocytosis of neuroblastoma cells
AbstractImmunotherapy with anti-GD2 monoclonal antibodies (mAbs) provides some benefits for patients with neuroblastoma (NB). However, the therapeutic efficacy remains limited, and treatment is associated with significant neuropathic pain. TargetingO-acetylated GD2 (OAcGD2) by 8B6 mAb has been proposed to avoid pain by more selective tumor cell targeting.  Thorough understanding of its mode of action is necessary to optimize this treatment strategy. Here, we found that 8B6-mediated antibody-dependent cellular phagocytosis (ADCP) performed by macrophages is a key effector mechanism. But efficacy is limited by upregulat...
Source: Cancer Immunology, Immunotherapy - January 1, 2022 Category: Cancer & Oncology Source Type: research

Anti-disialoganglioside antibody internalization by neuroblastoma cells as a mechanism of immunotherapy resistance
AbstractNeuroblastoma (NBL) accounts for a disproportionate number of deaths among childhood malignancies despite intensive multimodal therapy that includes antibody targeting disialoganglioside GD2, a NBL antigen. Unfortunately, resistance to anti-GD2 immunotherapy is frequent and we aimed to investigate mechanisms of resistance in NBL. GD2 expression was quantified by flow cytometry and anti-GD2 antibody internalization was measured using real-time microscopy in 20 human NBL cell lines. Neutrophil-mediated antibody-dependent cellular cytotoxicity (ADCC) assays were performed on a subset of the cell lines (n =&thin...
Source: Cancer Immunology, Immunotherapy - January 1, 2022 Category: Cancer & Oncology Source Type: research

Blocking GARP-mediated activation of TGF- β1 did not alter innate or adaptive immune responses to bacterial infection or protein immunization in mice
AbstractTransmembrane protein GARP binds latent TGF- β1 to form GARP:(latent)TGF-β1 complexes on the surface of several cell types including Tregs, B-cells, and platelets. Upon stimulation, these cells release active TGF-β1. Blocking TGF-β1 activation by Tregs with anti-GARP:TGF-β1 mAbs overcomes resistance to PD1/PD-L1 blockade and induces immun e-mediated regressions of murine tumors, indicating that Treg-derived TGF-β1 inhibits anti-tumor immunity. TGF-β1 exerts a vast array of effects on immune responses. For example, it favors differentiation of TH17 cells and B-cell switch to IgA pr...
Source: Cancer Immunology, Immunotherapy - January 1, 2022 Category: Cancer & Oncology Source Type: research

Local radiotherapy and E7 RNA-LPX vaccination show enhanced therapeutic efficacy in preclinical models of HPV16+ cancer
AbstractHuman papilloma virus (HPV) infection is a causative agent for several cancers types (genital, anal and head and neck region). The HPV E6 and E7 proteins are oncogenic drivers and thus are ideal candidates for therapeutic vaccination. We recently reported that a novel ribonucleic acid lipoplex (RNA-LPX)-based HPV16 vaccine, E7 RNA-LPX, mediates regression of mouse HPV16+ tumors and establishes protectiveTcell memory. An HPV16 E6/E7 RNA-LPX vaccine is currently being investigated in two phase I and II clinical trials in various HPV-driven cancer types; however, it remains a high unmet medical need for treatments for...
Source: Cancer Immunology, Immunotherapy - December 31, 2021 Category: Cancer & Oncology Source Type: research

Immune-related adverse events of COVID-19 vaccination in skin cancer patients receiving immune-checkpoint inhibitor treatment
AbstractTo date, few data are available regarding Adverse events (AEs) in cancer patients who are vaccinated for coronavirus disease 2019 (COVID-19) while being actively treated with Immune-checkpoint inhibitors (ICIs). We aimed to assess the safety of COVID-19 vaccines approved in Germany. Specifically, we investigated the frequency of general side effects and immune-related AEs of COVID-19 vaccination. A triage survey was used to collect the following information for patients with metastatic skin cancer: vaccine type, date of receipt of each dose of vaccine, and self-reported side effects. Clinical data were retrieved fr...
Source: Cancer Immunology, Immunotherapy - December 23, 2021 Category: Cancer & Oncology Source Type: research

Alterations of circulating lymphocyte subsets in patients with colorectal carcinoma
ConclusionWe found significant changes in circulating lymphocyte subsets in colon carcinoma patients, independent of physiological alterations due to gender or age. For some lymphocyte subsets significant differences according to tumor localization or MSI-status could be seen. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - December 20, 2021 Category: Cancer & Oncology Source Type: research

Correction to: Hepatotoxicity associated with PD-1 blockade antibodies in cancer patients co-infected with hepatitis B virus
(Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - December 6, 2021 Category: Cancer & Oncology Source Type: research

MAIT cells accumulate in ovarian cancer-elicited ascites where they retain their capacity to respond to MR1 ligands and cytokine cues
In conclusion, ascitic MAIT cells in EOC possess inducible effector functions that may be modified in future immunotherapeutic strategies. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - December 2, 2021 Category: Cancer & Oncology Source Type: research

Identification of prognostic genes in the pancreatic adenocarcinoma immune microenvironment by integrated bioinformatics analysis
ConclusionIn conclusion, this study demonstrates that PLAU may serve as a new diagnostic and therapeutic target, which is highly expressed in Chinese pancreatic cancer tissues and associated with lymph node metastasis.Graphical abstract (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - December 2, 2021 Category: Cancer & Oncology Source Type: research

Enhanced anti-melanoma efficacy through a combination of the armed oncolytic adenovirus ZD55-IL-24 and immune checkpoint blockade in B16-bearing immunocompetent mouse model
This study provides a rationale for investigation of such combination therapy in the clinic. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - November 6, 2021 Category: Cancer & Oncology Source Type: research

CD19 CAR-T cell treatment conferred sustained remission in B-ALL patients with minimal residual disease
In conclusion, pre-emptive CD19 CAR-T cell treatment is an effective and safe approach and may confer sustained remission in B-ALL patients with chemotherapy-refractory MRD. The trials were registered atwww.chictr.org.cn as ChiCTR-ONN-16009862 (November 14, 2016) and ChiCTR1800015164 (March 11, 2018). (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - November 6, 2021 Category: Cancer & Oncology Source Type: research

Exhaustion in tumor-infiltrating Mucosal-Associated Invariant T (MAIT) cells from colon cancer patients
AbstractMucosal-associated invariant T (MAIT) cells are unconventional T cells recognizing microbial metabolites, presented by the invariant MR1 protein. Upon activation, MAIT cells rapidly secrete cytokines and exert cytotoxic functions, and may thus be highly relevant also in tumor immunity. MAIT cells accumulate in colon tumors, but in contrast to other cytotoxic T cell subsets, their presence in tumors has been associated with worse patient outcome. Here we investigated if exhaustion may contribute to reduced anti-tumor immunity by MAIT cells. Freshly isolated lymphocytes from colon tumors, unaffected tissue and blood ...
Source: Cancer Immunology, Immunotherapy - November 6, 2021 Category: Cancer & Oncology Source Type: research

CD16xCD33 Bispecific Killer Cell Engager (BiKE) as potential immunotherapeutic in pediatric patients with AML and biphenotypic ALL
AbstractSimilar to pediatric acute myeloid leukemia (AML) the subgroup of biphenotypic acute lymphoblastic leukemia (ALL) is a rare complex entity with adverse outcome, characterized by the surface expression of CD33. Despite novel and promising anti-CD19 targeted immunotherapies such as chimeric antigen receptor T cells and bispecific anti-CD19/CD3 antibodies, relapse and resistance remain a major challenge in about 30% to 60% of patients. To investigate the potential role of the fully humanized bispecific antibody CD16  × CD33 (BiKE) in children with CD33+ acute leukemia, we tested whether the reagent...
Source: Cancer Immunology, Immunotherapy - November 6, 2021 Category: Cancer & Oncology Source Type: research

Nutrient supplements from selected botanicals mediated immune modulation of the tumor microenvironment and antitumor mechanism
AbstractSpecific extracts of  selected vegetables (SV) have been shown to benefit the survival of stage IIIb/IV non-small cell lung cancer patients in phase I/II studies and is currently in a phase III trial. However, the underlying mechanism of SV-mediated antitumor immune responses has not been elucidated. Our results indica te that SV modulated the NK and adoptive T cell immune responses in antitumor efficacy. Furthermore, antitumor effects of SV were also mediated by innate myeloid cell function, which requires both TLR and β-glucan signaling in a MyD88/TRIF and Dectin-1-dependent manner, respectively. Additi...
Source: Cancer Immunology, Immunotherapy - November 6, 2021 Category: Cancer & Oncology Source Type: research

Human hydatid cyst fluid-induced therapeutic anti-cancer immune responses via NK1.1+ cell activation in mice
AbstractEchinococcus granulosus is a cestode parasite which causes cystic echinococcosis disease. Previously we observed that vaccination withE. granulosus antigens from human hydatid cyst fluid (HCF) significantly inhibits colon cancer growth. In the present work, we evaluate the anti-tumor immune response induced by human HCF against LL/2 lung cancer in mice. HCF vaccination protected from tumor growth, both in prophylactic and therapeutic settings, and significantly increased mouse survival compared to control mice. Considering that tumor-associated carbohydrate antigens are expressed inE. granulosus, we oxidized termin...
Source: Cancer Immunology, Immunotherapy - November 6, 2021 Category: Cancer & Oncology Source Type: research

Blood tumor mutation burden can predict the clinical response to immune checkpoint inhibitors in advanced non-small cell lung cancer patients
AbstractBackgroundTissue tumor mutation burden (tTMB) assessed by whole-exome sequencing (WES), which has been regarded as the gold standard method of tTMB measurement, can predict the clinical benefits of immune checkpoint inhibitors (ICIs). Multiple studies have investigated the feasibility of utilizing large panels to evaluate TMB but have obtained conflicting results. Furthermore, whether blood TMB (bTMB) can also be a predictive biomarker in NSCLC has not been determined.MethodsFifty-six advanced NSCLC patients treated with ICIs were enrolled, including an exploratory cohort (n = 42) and a small independ...
Source: Cancer Immunology, Immunotherapy - November 6, 2021 Category: Cancer & Oncology Source Type: research

The PI3K δ inhibitor idelalisib impairs the function of human dendritic cells
AbstractThe PI3K δ-inhibitor Idelalisib is approved for the treatment of Non-Hodgkin lymphoma. However, its use has been decreased within the last years due to deleterious infections such as cytomegalovirus and pneumocystis jirovecii. Here, we have investigated the effect of Idelalisib on human monocyte-derived den dritic cells (DCs) as important players in the induction of immune responses. We found that Idelalisib-treated DCs displayed impaired T cell stimulatory function. PI3Kδ inhibition during differentiation resulted in decreased Interleukin-12, Interleukin-13 and TNFα production by DCs after lipopo...
Source: Cancer Immunology, Immunotherapy - November 6, 2021 Category: Cancer & Oncology Source Type: research

A prime/boost vaccine platform efficiently identifies CD27 agonism and depletion of myeloid-derived suppressor cells as therapies that rationally combine with checkpoint blockade in ovarian cancer
AbstractCancer immunotherapies have generated remarkable clinical responses for some patients with advanced/metastatic disease, prompting exploration of rational combination therapies to bolster anti-tumor immunity in patients with limited response or those who experience tumor progression following an initial response to immunotherapy. In contrast to other tumor indications, objective response rates to single-agent PD-1/PD-L1 blockade in ovarian cancer are limited, suggesting a need to identify combinatorial approaches that lead to tumor regression in a setting where checkpoint blockade alone is ineffective. Using a pre-c...
Source: Cancer Immunology, Immunotherapy - November 6, 2021 Category: Cancer & Oncology Source Type: research

Interruption of MDM2 signaling augments MDM2-targeted T cell-based antitumor immunotherapy through antigen-presenting machinery
In this report, we identified an MDM2-derived peptide epitope (MDM232-46) that elicited antigen-specific and tumor-reactive CD4+ T cell responses. These CD4+ T cells directly killed tumor cells via granzyme B. MDM2 is expressed in head and neck cancer patients with poor prognosis, and the T cells that recognize this MDM2 peptide were present in these patients. Notably, Nutlin-3 (MDM2-p53 blocker), inhibited tumor cell proliferation, was shown to augment antitumor T cell responses by increasing MDM2 expression, HLA-class I and HLA-DR through class II transactivator (CIITA). These results suggest that the use of this MDM2 pe...
Source: Cancer Immunology, Immunotherapy - November 6, 2021 Category: Cancer & Oncology Source Type: research

COM902, a novel therapeutic antibody targeting TIGIT augments anti-tumor T cell function in combination with PVRIG or PD-1 pathway blockade
AbstractImmune checkpoint inhibitors (ICIs) have emerged as promising therapies for the treatment of cancer. However, existing ICIs, namely PD-(L)1 and CTLA-4 inhibitors, generate durable responses only in a subset of patients. TIGIT is a co-inhibitory receptor and member of the DNAM-1 family of immune modulating proteins. We evaluated the prevalence of TIGIT and its cognate ligand, PVR (CD155), in human cancers by assessing their expression in a large set of solid tumors. TIGIT is expressed on CD4+ and CD8+ TILs and is upregulated in tumors compared to normal tissues. PVR is expressed on tumor cells and tumor-associated m...
Source: Cancer Immunology, Immunotherapy - November 6, 2021 Category: Cancer & Oncology Source Type: research