IFNG elevation

The silencing of caspase-4 confirmed the regulatory role of GBP1 in MB cell pyroptosis. Our findings suggest that NDV elevates IFN-g and GBP1 expression in MB cells, potentially contributing to caspase-4-mediated pyroptosis activation.

Effector T cell infiltration is enhanced in tumours derived from cells pre-treated with IFNγ in immunocompetent female mice when PARP14 is pharmacologically inhibited or knocked down, while the presence of regulatory T cells is decreased, leading to restoration of α-PD-1 sensitivity. Finally, we determine that tumours which spontaneously relapse in immunocompetent female mice following α-PD-1 therapy upregulate IFNγ signalling and can also be re-sensitised upon receiving PARP14 inhibitor treatment, establishing PARP14 as an actionable target to reverse IFNγ-driven ICBT resistance.

Knockdown or pharmacological inhibition of PARP14 increased effector T cell infiltration into tumors derived from cells pre-treated with IFNγ and decreased the presence of regulatory T cells, leading to restoration of α-PD-1 sensitivity. Finally, we determined that tumors which spontaneously relapsed following α-PD-1 therapy could be re-sensitized upon receiving PARP14 inhibitor treatment, establishing PARP14 as an actionable target to reverse IFNγ-driven ICBT resistance.

Overall, the present in vitro data suggested that CIK cells exerted a cytotoxic function in B-NHL cells, and a combination of PD-1 inhibitors with CIK cells may provide a potential therapeutic option for this type of lymphoma. Nevertheless, in vivo experiments are warranted to undermine the extent to which PD-1 inhibitors may be used to enhance the antitumor activity of CIK cells in B-NHL.

ASK1 deficiency augmented cytokine production chemoattractive to NK cells possibly through induction of the ligand for NKG2D, a key activating receptor of NK cells, leading to further recruitment of NK cells into the lung. These results indicate that ASK1 negatively regulates NK cell-dependent anti-tumor immunity and that ASK1-targeted therapy can provide a new tool for cancer immunotherapy to overcome tumor metastasis.

These therapeutic benefits including decreased PD-L1 expression, alleviated T cell exhaustion, and reversed tumor hypoxia successfully suppressed both the primary and abscopal tumor growth in bladder and colon cancers, respectively. Combining with its excellent biocompatibility, our results indicate that this IR775@Met@Lip system has great potential to become a highly effective cancer therapy modality.

Cured mice are also protected against tumor re-challenge due to a CD8-dependent protective response. Hence, combination treatment of small-molecule P2RX7 activator followed by immune checkpoint inhibitor represents a strategy that may be active against NSCLC.

In human breast cancer, the frequency of CD39PD-1CD8 but not total CD8 T cells correlates with delayed metastatic relapse after resection (disease-free survival), thus underlining the biological relevance of CD39PD-1CD8 T cells for controlling experimental and human breast cancer. Thus, we suggest that a primary breast tumor could prime a systemic, CD39PD-1CD8 T cell response that favors metastatic dormancy in the lungs.

We suggest that multiple infusions of high dose allogeneic prenatal MSCs are safe and can rapidly improve respiratory distress and reduce inflammatory biomarkers in some critically ill COVID-19-induced ARDS cases. Patients that develop sepsis or multi-organ failure may not be good candidates for stem cell therapy. Large randomized multicenter clinical trials are needed to discern the exact therapeutic potentials of MSC in COVID-19-induced ARDS.

The results confirm the immunomodulatory activity of AL in humans. This activity, in complementary with the direct action of AL on inducing cholangiocarcinoma cell apoptosis, suggests its potential role for CCA control.

In view of the role played by IFN overexpression in the development and progression of pSS, inhibition or modulation of IFN signaling has been regarded as a potential target for the therapeutic approach. A number of therapeutic compounds with variable mechanisms of action have been tested or are under consideration for the treatment of patients with pSS.

In addition, lower levels of IL-7 were found in patients harboring BRAF mutants. These findings indicate that these cytokines may play critical roles in the progression of melanoma.

The combined therapy increased the number of tumor-infiltrating IFN-γ/TNF-α-producing CD4 and CD8 T cells and delayed tumor growth, as compared to the effect observed in groups treated with c-di-GMP or IRE alone. These results can lead to the development of a new therapeutic strategy for the treatment of cancer patients refractory to other therapies.

Consequently, significantly lower tumor sizes and prolonged survival time were detected in F4d and F4e subgroups compared to control after challenging mice with 4T1 cells. Accordingly, these results demonstrated that PBMCs pulsed F4 peptide-based vaccine could induce a protective immune response while it is a simple and less expensive vaccine.

Our results show that PCa pTA-NKs acquire properties related to the pro-inflammatory angiogenesis in endothelial cells, recruit monocytes and polarize macrophage to an M2-like type phenotype. Our data provides a rationale for a potential use of pNK profiling in PCa patients.

Despite a correlation with the number of intra-tumoral CD8 T cells, tumoral JAK1 expression as a surrogate marker for IFN-γ signaling was not associated with HLA-I/APM expression. Thus, the presented findings strongly indicate the presence of additional factors involved in the immunomodulatory process of HPV-negative OSCC with a possible tumor-burden-dependent complex network of immune escape mechanisms beyond HLA-I/APM components and T cell infiltration in this tumor entity.

In contrast, interfering with nontumor/host cell Tnfrsf1a led to cure in 100% of animals following agonistic αCD40+αPD-L1 and promoted the formation of circulating central memory T cells rather than long-lived effector T cells. In summary, we identify a mechanistic basis for T cell exhaustion in pancreatic cancer and a feasible clinical strategy to overcome it.

In conclusion, high levels of Tim-3 and Galectin-9 in HPV positive cervical cancer patients play roles in the progression of disease by promoting Treg cells to inhibit the cytotoxic function of Th1 and CD8+ T cells. Tim-3/Galectin-9 may serve as a new immunotherapy target for patients with HPV positive cervical cancer.

The results indicate that low dose CPT and TPT could be repurposed to treat lupus nephritis.

We observed that mice vaccinated with Lip-DOPE-P5+435 formulation had the highest number of IFN-γ- producing CTLs with the highest cytotoxic activity that consequently led to significantly smallest tumor size and prolonged survival rate in the TUBO mice model. In conclusion, our study indicated that the liposomal form of P5+435 peptide containing DOPE can be regarded as a promising prophylactic anti-cancer vaccine to generate potent antigen-specific immunity.

These variations are evident through all tumor stages and suggest that a deficiency in γδ T cell populations could be preventing control of tumor progression. This fact prove the role of immunomodulation on CC carcinogenesis.

Our data suggest that these cells may play a critical role in the pathophysiology of ICI-related pulmonary complications. Understanding of these cell populations may also provide predictive and diagnostic biomarkers of ICI-related pulmonary complications, eventually enabling differentiation of pneumonitis from pneumonia in AML/MDS patients receiving ICI-based therapies.

Furthermore, the increase in the number of immune cells was accompanied by increased pro-inflammatory cytokines interleukin-12 (IL-12), interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and decreased suppressive cytokine IL-10. The results indicate that Nr-CWS, as an immunotherapeutic agent for HR-HPV infection and CIN, plays an immune promoting role related to the upregulation of T cell subsets and the inhibition of PD-1/PD-L1 pathway.

In addition, increased expression of DCC and A2BAR, and decreased expression of UNC5B, UNC5C and DSCAM were found in endometriotic lesions. These results suggest that netrin-1 production by macrophages in endometriotic lesions may play an important role in endometriosis-associated pain.

The ITI regimen can raise the ratio of CD4/CD8 T cells and the percentage of natural killer cells, also, can enhance the generation of perforin and granzyme B and the concentration of IFN-γ as well as inhibit the generation of VEGF, suggesting that these activities may enhance the antitumour capacity of patients with AML.

The HLDF effect on the cytokine production by the tumor and its microenvironment was different in ND patients and IBC-NST patients. HDLF suppressed IFN-γ production in the pooled group of IBC-NST patients; HLDF mainly had a suppressive effect on the production of IL-6, IL-8, TNF-α, GM-CSF and MCP-1 in IBC-NST patients of group IIA.

Understanding these responses may unveil potential therapeutic targets to enhance radiation response and mitigate normal tissue injury. Tumour irradiation in this cohort enhances innate immune responses, which may be harnessed to improve patient treatment outcome.

Here, we identified an immunosuppression signature (IMS) through analyzing RNA sequencing data from a combined discovery cohort (n = 120) consisting of three publicly available melanoma datasets. Using the ratio of an established IFN-γ signature and IMS led to consistently better prediction of the ICI therapy outcome compared to a collection of nine published GEP signatures from the literature on a newly generated internal validation cohort (n = 55) and three published datasets of metastatic melanoma treated with anti-PD-1 (n = 54) and anti-CTLA-4 (n = 42), as well as in patients with gastric cancer treated with anti-PD-1 (n = 45), demonstrating the potential utility of IMS as a predictive biomarker that complements existing GEP signatures for immunotherapy.

Zingerone improve the T cell-mediated and antibody responses in a mouse model of breast cancer. The immunotherapeutic potentials of zingerone in cancers need more considerations.

Tumor immunotherapy models targeting at paired Ig-like receptor B (PIR-B, an ortholog of ILT4 in mouse)/ILT4 and/or PD-L1 were established in C57BL/6 mice inoculated with stable EGFR- overexpressing Lewis lung carcinoma (LLC) cells and in humanized NSG mice inoculated with EGFR mutant, gefitinib-resistant PC9 (PC9-GR) or EGFR-overexpressing wild type H1299 cells...Furthermore, ILT4 inhibition enhanced the efficacy of PD-L1 inhibitor in EGFR wild-type but not in EGFR mutant NSCLC. Our study identified novel mechanisms for EGFR-mediated tumor immune escape, and provided promising immunotherapeutic strategies for patients with EGFR-activated NSCLC.

In conclusion, TIL products from RCC lesions contain tumor-reactive Tcells. Their restricted tumor-specific cytokine production requires further investigation of immunosuppressive factors in RCC and subsequent optimization of RCC-derived TIL culture conditions.

The combination treatment led to trigger immunogenic tumor apoptosis, and enhance antitumor immunity, therefore, improved anti-tumor efficiency, and further prolonged survival duration. The combination of liposomal silybin and liposomal doxorubicin might be a new chemo-immunotherapy approach for triple negative breast cancer (TNBC) tumor treatment.

 With limited patients, axi-cel retreatment showed high responses in patients with R/R iNHL. Safety profiles and CAR T cell expansion were similar at retreatment and first treatment; tumor burden was lower before retreatment. Confirmatory analyses are needed.

 With limited patients, axi-cel retreatment showed high responses in patients with R/R iNHL. Safety profiles and CAR T cell expansion were similar at retreatment and first treatment; tumor burden was lower before retreatment. Confirmatory analyses are needed.

 With limited patients, axi-cel retreatment showed high responses in patients with R/R iNHL. Safety profiles and CAR T cell expansion were similar at retreatment and first treatment; tumor burden was lower before retreatment. Confirmatory analyses are needed.

 With limited patients, axi-cel retreatment showed high responses in patients with R/R iNHL. Safety profiles and CAR T cell expansion were similar at retreatment and first treatment; tumor burden was lower before retreatment. Confirmatory analyses are needed.

Here, we present ZUMA-2 results by MCL morphology and prior BTKi exposure (ibrutinib and/or acalabrutinib), accompanied by basic product attribute characterization.  All subgroups drew clinical benefit from KTE-X19 treatment despite some pharmacological differences. Clinical Trial Registry: NCT02601313; https://clinicaltrials.gov/ct2/show/NCT02601313

Patients in C6 received dexamethasone 10 mg orally on Days 0 (before axi‑cel), 1, and 2 and earlier intervention with corticosteroids and tocilizumab.  Prophylactic corticosteroid use resulted in no Grade ≥3 CRS, a low Grade ≥3 NE rate, and delayed CRS onset, without affecting median peak CAR T-cell levels or responses. Differences in cohort sizes and baseline characteristics should be considered when comparing cohorts. Longer follow-up is required to determine the impact on response duration and survival.