Dendritic cell-based cancer immunotherapy in the era of immune checkpoint inhibitors: From bench to bedside

Ghorbaninezhad, Farid; Asadzadeh, Zahra; Masoumi, Javad; Mokhtarzadeh, Ahad; Kazemi, Tohid; Aghebati‐Maleki, Leili; Shotorbani, Siamak Sandoghchian; Shadbad, Mahdi Abdoli; Baghbanzadeh, Amir; Hemmat, Nima; Bakhshivand, Mohammad; Baradaran, Behzad

doi:10.1016/j.lfs.2022.120466

Cited by 22 publications

(13 citation statements)

References 254 publications

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“…αCTLA-4 was combined with antigen-loaded autologous DCs aiming to block the inhibitory signaling mediated by the injected autologous DCs and augment the T cell priming response. 26 …”

Section: Discussionmentioning

confidence: 99%

Intratumoral administration of pro-inflammatory allogeneic dendritic cells improved the anti-tumor response of systemic anti-CTLA-4 treatment via unleashing a T cell-dependent response

et al. 2022

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Immune checkpoint inhibitors (ICIs) have revolutionized the oncology field. However, a significant number of patients do not respond, at least partly due to the lack of preexisting anti-tumor T-cell immunity. Therefore, it is emergent to add an immune-priming step to improve efficacy. Here, we report a combined approach consisting of intratumoral administration of pro-inflammatory allogeneic dendritic cells (AlloDCs) and systemic treatment with αCTLA-4 that can drastically improve the anti-tumor efficacy compared to αCTLA-4 monotherapy. When evaluated in mice with large established CT-26 tumors, monotherapy with αCTLA-4 neither delayed tumor progression nor improved mice survival. However, combination treatment of AlloDCs and αCTLA-4 drastically improved the effectiveness, with 70% of mice being cured. This effect was T cell-dependent, and all survived mice rejected a subsequent tumor re-challenge. Further investigation revealed an immune-inflamed tumor microenvironment (TME) in the combination treatment group characterized by enhanced infiltration of activated antigen-presenting endogenous DCs and CD8 + T cells with a tissue-resident memory (T RM ) phenotype (CD49a + CD103 + ). This correlated with elevated levels of tumor-specific CD39 + CD103 + CD8 + T cells in the tumor and “tumor-matching” NKG2D + CD39 + CX3CR1 + CD8 + T cells in peripheral blood. Moreover, splenocytes from mice in the combination treatment group secreted significantly higher IFN-γ upon stimulation with the peptide from the endogenous CT-26 retroviral gp70 (model neoantigen), confirming the induction of a tumor-specific CD8 + T-cell response. Taken together, these data indicate a strong anti-tumor synergy between AlloDCs and αCTLA-4 that warrant further clinical investigation with the corresponding human AlloDC product (ilixadencel) for patients receiving αCTLA-4 therapy.

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“…αCTLA-4 was combined with antigen-loaded autologous DCs aiming to block the inhibitory signaling mediated by the injected autologous DCs and augment the T cell priming response. 26 …”

Section: Discussionmentioning

confidence: 99%

Intratumoral administration of pro-inflammatory allogeneic dendritic cells improved the anti-tumor response of systemic anti-CTLA-4 treatment via unleashing a T cell-dependent response

et al. 2022

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“…Although immune checkpoint blockers (ICBs), which primarily target cytotoxic T lymphocytes, are widely used in current clinical practice ( 40 , 41 ), TAMs and DCs have also been favored and explored in recent decades. A variety of therapeutic strategies targeting TAMs and DCs are being tested in basic researches and clinical trials ( 42 , 43 , 44 ), for example, inhibiting mononuclear macrophage recruitment, TAM depletion and inhibition of activation, reprogramming TAMs and DC-based cancer vaccines. Correspondingly, a variety of relevant molecules are being targeted, for instance, blockade of CD47 to enhance the phagocytotic abilities of antigen-presenting cells, inhibition of phosphoinositide 3-kinase γ (PI3Kγ) to interrupt M2 polarization, and Toll-like receptor (TLR) agonists to induce M1 polarization.…”

Section: Discussionmentioning

confidence: 99%

EPSTI1 as an immune biomarker predicts the prognosis of patients with stage III colon cancer

Wang

Cheng²,

Zeng³

et al. 2022

Front. Immunol.

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ObjectiveThe poor prognosis and heterogeneity of stage III colon cancer (CC) suggest the need for more prognostic biomarkers. The tumor microenvironment (TME) plays a crucial role in tumor progression. We aimed to explore novel immune infiltration-associated molecules that serve as potential prognostic and therapeutic targets.MethodsTME immune scores were calculated using “TMEscore” algorithm. Differentially expressed genes between the high and low TME immune score groups were identified and further investigated through a protein-protein interaction network and the Molecular Complex Detection algorithm. Cox regression, meta-analysis and immunohistochemistry were applied to identify genes significantly correlated with relapse-free survival (RFS). We estimated immune infiltration using three different algorithms (TIMER 2.0, CIBERSORTx, and TIDE). Single-cell sequencing data were processed by Seurat software.ResultsPoor RFS was observed in the low TME immune score groups (log-rank P < 0.05). EPSTI1 was demonstrated to be significantly correlated with RFS (P < 0.05) in stage III CC. Meta-analysis comprising 547 patients revealed that EPSTI1 was a protective factor (HR = 0.79, 95% CI, 0.65-0. 96; P < 0.05)). More immune infiltrates were observed in the high EPSTI1 group, especially M1 macrophage and myeloid dendritic cell infiltration (P < 0.05).ConclusionThe TME immune score is positively associated with better survival outcomes. EPSTI1 could serve as a novel immune prognostic biomarker for stage III CC.

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“…DCs also infiltrate the TME but quickly adapt regulatory or tolerogenic phenotypes that promote tumor growth and immunoevasion [ 163 , 164 , 165 ]. Conventional DC types 1 (cDC1) and 2 (cDC2) play a key role as APCs and activate T cells for antitumor responses [ 166 , 167 , 168 ]. cDC1s and cDC2s in the TME are associated with a good prognosis in various cancers, while plasmacytoid DCs (pDC) frequencies are associated with a worse PFS and OS [ 169 , 170 , 171 , 172 , 173 ].…”

Section: Basic Research In Cancer Immunologymentioning

confidence: 99%

Recent Advances and Challenges in Cancer Immunotherapy

Peterson

Denlinger

Yang

2022

Cancers

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Cancer immunotherapy has revolutionized the field of oncology in recent years. Harnessing the immune system to treat cancer has led to a large growth in the number of novel immunotherapeutic strategies, including immune checkpoint inhibition, chimeric antigen receptor T-cell therapy and cancer vaccination. In this review, we will discuss the current landscape of immuno-oncology research, with a focus on elements that influence immunotherapeutic outcomes. We will also highlight recent advances in basic aspects of tumor immunology, in particular, the role of the immunosuppressive cells within the tumor microenvironment in regulating antitumor immunity. Lastly, we will discuss how the understanding of basic tumor immunology can lead to the development of new immunotherapeutic strategies.

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Dendritic cell-based cancer immunotherapy in the era of immune checkpoint inhibitors: From bench to bedside

Cited by 22 publications

References 254 publications

Intratumoral administration of pro-inflammatory allogeneic dendritic cells improved the anti-tumor response of systemic anti-CTLA-4 treatment via unleashing a T cell-dependent response

Intratumoral administration of pro-inflammatory allogeneic dendritic cells improved the anti-tumor response of systemic anti-CTLA-4 treatment via unleashing a T cell-dependent response

EPSTI1 as an immune biomarker predicts the prognosis of patients with stage III colon cancer

Recent Advances and Challenges in Cancer Immunotherapy

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