CXCL9 expression

Our study illustrates that the tumor immune microenvironment prior to CPI treatment can be indicative of response. In perspective, modulating the myeloid and/or effector cell compartment by altering the described cell interactions and transitions could improve immunotherapy response.

The seven-gene signature holds promise as a valuable tool for decision-making and prognosis prediction in patients with ovarian cancer.

Finally, using The Cancer Genome Atlas database, we found that XCL1 expression was positively correlated with tumor-infiltrating cDC1s and a better prognosis in melanoma patients. Collectively, our findings provide a novel therapeutic approach to enhance tumor-specific CTL responses through the selective recruitment of CXCL9-expressing cDC1s into the tumor masses.

With this strategy, it is efficient encapsulation and release of multiple drug loads that can efficiently induce CXCL9 expression in macrophages, both in vitro and in vivo in a mouse tumor model. These observations provide a window into the molecular features that define TAM-specific states, an insight a novel therapeutic anticancer approach is used to discover.

Symptomatic BPH with immune-enriched landscapes may support anti-tumor immunity. RNA sequencing of benign prostate biopsy tissue showing upregulation of NKX3-1 and HOXB13 with the absence of T-cells might help in identifying men at higher risk of future PCa development, which may be useful in determining ongoing PCa screening.

Such data suggest these cells might also increase immunosuppressive interactions with T cells. In summary, our study reveals how ICB affects the spatial architecture and crosstalk of different cell types within melanoma brain metastases and will provide insights into new therapeutic strategies for brain metastases patients.

Background: Cevostamab is an FcRH5 (Fc receptor-homolog 5) targeted T cell-dependent bispecific (TDB) currently being evaluated in the clinic, with promising activity and favorable safety profile as a monotherapy in patients (pts) with heavily pre-treated Relapsed/Refractory multiple myeloma (MM) (NCT03275103, Trudel et al... We first examined the T cell compartment by scRNA-seq profiling. Upon FcRH5 TDB treatment, clustering analysis suggested that CD4 and CD8 T cells undergo extensive transcriptional changes compared to control TDB (Fig 1A). A TNF and LTA-expressing CD4 memory cluster was enriched upon treatment in both SoRs and Rs, but to a greater extent in Rs.

P2, N=50, Completed, Emma Guttman | Active, not recruiting --> Completed

Conclusions We identified CCL2 and galectin-3 as tumor factors regulated by K17 expression. Validation studies are needed to confirm their protein expressions and their direct role in tumor-macrophage communications.

Whereas MC1R activation is restricted to melanoma, GNAS activation by hotspot mutations is observed across diverse cancer types and is associated with reduced CXCL9/10/11 expression. Our study implicates MC1R as a melanoma immunotherapy target and suggests GNAS-PKA signaling as a pan-cancer oncogenic pathway inhibiting antitumor T cell response.

The analyses from TCGA cohort (n=138) showed that elevated CXCL9 expression correlated with increased infiltration of B-cells, macrophages, natural killer cells, monocytes and increased expression of immune checkpoint molecules and other CXCL family members, including CXCL10 and CXCL11. These findings confirm the regulatory role of CXCL9 in antitumor immunity and suggest a potential role in treatments involving immune-checkpoint blockade.

In patients with OC, the radiomics signature(RS) of CT scans can distinguish the level of CXCL9 expression and predict prognosis, potentially fulfilling the ultimate purpose of precision medicine.

P=N/A, N=20, Recruiting, Centre Hospitalier Universitaire de Nice | Trial completion date: Dec 2024 --> Jun 2025 | Trial primary completion date: Dec 2024 --> Jun 2025

This study ascribes for a new immunomodulatory role for IL11 during tumor development that is amenable to anti-cytokine based therapy of colon cancer.

This coordinated chemokine switch led to increased T-cell infiltration in an in vitro chemotaxis assay. Our study demonstrates that CAFs have a phenotypic plasticity that allows their adaptation to contrasting immune tissue microenvironments.

This chemokine system is also likely to contribute to tissue necrosis, which is a signature histological feature of DLBCL-CI. Further studies are warranted to determine whether the CXCL9-CXCL10/CXCR3 axis exerts antitumor effects in DLBCL-CI.

This coordinated chemokine switch led to increased T-cell infiltration in an in vitro chemotaxis assay. Our study demonstrates that CAFs have a phenotypic plasticity that allows their adaptation to contrasting immune tissue microenvironments.

Moreover, specific co-expression of CXCL9 and αPD-L1 in various tumor cells is achieved by replacing the tyrosinase promoter of NP with a survivin promoter, which increases T-cell infiltration and activation and therapeutic efficacy in multiple tumors in female mice. This study provides a strategy to maximize the immunotherapeutic outcome regardless of the heterogeneous tumor microenvironment.

Overexpressed CXCL9 correlates with antitumor immunity and is predictive of a favorable prognosis in UCEC. It hinted that CXCL9 may serve as an independent prognostic biomarker or therapeutic target in UCEC patients, which augmented anti-tumor immune effects to furnish survival benefits.

In T-cell acute lymphoblastic leukemia, chidamide may increase the concentration of CXCL9 in the tumor microenvironment by up-regulating the expression of CXCL9 in tumor cells, leading to an increase in the number of CD8 T cells.

P=N/A, N=20, Recruiting, Centre Hospitalier Universitaire de Nice | Trial primary completion date: Jun 2023 --> Dec 2024

Therefore, RT potentially activates CD8 T cells by inducing IFNs-mediated CXCL10 and ICAM-1 expression in tumors to enhance CD8 T-tumor adhesion and recognition. This study clarified the possible mechanisms of RT and IFNs in regulating CD8 T cell activation in lung cancer.

These findings indicate that CXCL9 is a potential clinical biomarker of prognosis and immunotherapy efficacy for TNBC patients. Also, it stimulates JAK/STAT activity, which in turn modifies the tumor microenvironment.

Glioma cell proliferation and invasion could be inhibited by silencing of CXCL9. Overall, CXCL9 is correlated to the prognosis of glioma patients and may accelerate glioma development via immune regulation.

High CXCL9 expression correlated with increased infiltration levels of immune cells in the TME, including CD8+ T lymphocytes and M1 macrophages. These findings suggest that high PD-L1 expression is a prognostic factor of early-stage CRC, and CXCL9 may play a key role in regulating PD-L1 expression.

SRC-3 is a critical immunomodulator in breast cancer, generating a protumor immune microenvironment. SRC-3 inhibition by SI-2 or SRC-3 KD activates the Cxcl9/Cxcr3 axis in breast tumors and enhances the antitumor immune microenvironment to suppress breast cancer progression.

We hypothesized that the combination of CKM with paclitaxel will promote selective CTL infiltration into TNBC, and along with doxorubicin/cyclophosphamide (AC), will result in higher rate of pCR, translating into improved RFS and OS. The treatment was well-tolerated and no DLTs were observed and we determined RP2D for future studies. We observed promising clinical activity with pCR + ypTmic rate of 66%, comparable to pembrolizumab combination with NAC. A larger phase II study is being designed to confirm the observed efficacy and to determine if CKM regimen would be a safer short-term alternative to pembrolizumab or if CKM can overcome the resistance to the standard pembrolizumab/NAC therapy.

A wide characterization (chemokine receptors, factors involved in pancreatic organogenesis, markers of epithelial-mesenchymal transition, and secretome) revealed that the degree of stemness was associated with KRT19 and NKX2.2 mRNA expression, with CD49a and CA19.9/Tie2 protein expression, and with the secretion of VEGF, IL-7, IL-12p70, IL-6, CCL3, IL-10, and CXCL9. The expression of stem cell markers was also evaluated on primary tumor cells from 55 PDAC patients who underwent pancreatectomy with radical intent, revealing that CXCR4/CD133 and CD24 cells, but not ESACD24CD44, are independent predictors of mortality.

Our results demonstrate that intratumoral administration of PC7A nanovaccine achieved stronger antitumor immunity and efficacy over subcutaneous injection. These data suggest intratumoral administration should be included in the therapeutic design in the clinical use of nanovaccine.

CXCL9 is a driver of successful ICB in preclinical ovarian cancer. Besides being a feasible predictive biomarker, CXCL9-inducing agents thus represent attractive combination partners to improve ICB in this cancer entity.

P=N/A, N=20, Recruiting, Centre Hospitalier Universitaire de Nice | Not yet recruiting --> Recruiting | Trial completion date: Jan 2024 --> Dec 2024 | Initiation date: Jul 2021 --> Dec 2021 | Trial primary completion date: Jul 2021 --> Jun 2023

Interestingly, we observed a high concordance between mouse and human myeloid cells from ours and publicly available scRNA-Seq data. Our data and analysis provide the first translational mouse-to-human atlas of myeloid cells in HNC, providing a way to inform biomarkers and immunotherapeutic targets for potential ICI therapy success in HNC and other cancer types.

Additionally, CART-CXCL9 cell therapy slowed tumor growth and prolonged mouse survival, displaying superior antitumor activity. Briefly, modifying CAR T cells to express CXCL9 could effectively improve CAR T cell efficacy against solid tumors.

We will also present a novel bioinformatics analysis to interrogate how cell-cell signaling interactions between myeloid and T cell subsets influence their downstream gene regulatory network and tumor immune phenotypes. This analysis provides a reference for future studies in HNC immunology.

The immune biomarker gene set was subject to significantly more intra tumour heterogeneity of expression (Mean RNA-ITH Score 0.50 vs 0.31 p=6.4e-12).In conclusion we demonstrate significant heterogeneity of immune biomarkers in NSCLC and in particular a lack of robustness of expression-based predictors of response to immunotherapy. This highlights the need for biomarkers that are robust to intra-tumour heterogeneity and sampling bias or the need for more representative tumour sampling techniques.

Using RT-qPCR, we observed that, compared to CRT, MRT, up to the dose that we applied, significantly increased and did not saturate CXCL9 expression, a cytokine that plays a crucial role in the attraction of activated T cells. Finally, MRT combined with anti-CTLA-4 ablated the tumor in half of the cases, and induced prolonged systemic antitumor immunity.

Our studies demonstrate that PTPN2 deficiency in tumour cells drives STAT-1 signalling and thereby T cell recruitment, PD-L1 expression and enhances the response to immunotherapy. Moreover, the combinatorial targeting of PTPN2 in tumour and T cells can yield added benefit by alleviating inhibitory constraints on recruited or pre-existing T cells to combat TNBC.

A nuclear imaging platform by In-labeled nivolumab was used to track CD8 T cells homing to tumors in vivo...We demonstrated that IR induced IFNα and CXCL9 expression in A549 cells, leading to CD8 T cell migration. This study unveiled a potential mechanism for radiotherapy to activate and recruit CD8 T cells to suppress lung tumors.

This work proposed a promising biomarker for evaluating TME immune characteristics and clinical outcomes in patients with ovarian cancer. Estimation of CXCL10 risk pattern sheds a novel insight on ovarian cancer TME immune characteristics and provides strategies for ovarian cancer immunotherapy.

Overall, the proportion of immune-rich/poor tumors differed by subtype; however, a subset of 10 LM22 genes that marked immune-rich status remained the same across subtype. Non-LM22 genes differentially expressed between the phenotypes suggest that the biologic processes responsible for immune-poor phenotype are not yet well characterized.