Coley's immunotherapy revived: Innate immunity as a link in priming cancer cells for an attack by adaptive immunity

Uher, Ondřej; Caisová, Veronika; Hansen, Per; Kopecký, Jan; Chmelař, Jindrǐch; Zhuang, Zhengping; Zenka, Jan; Pacák, Karel

doi:10.1053/j.seminoncol.2019.10.004

Cited by 13 publications

(19 citation statements)

References 69 publications

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“…In addition, the dendritic cells produce costimulatory molecules and present antigen from a patient's cancer cells to promote proliferation of tumor-specific cytotoxic CD8+ T cells. These T cells then migrate to tumor sites, displaying their tumor-killing effects during the effector phase (29)(30)(31)(193)(194)(195). According to this mechanism, combination therapy including a TLR9 agonist and immune inhibitor is promising because these two agents use different and complementary mechanisms to up-regulate the T-cell-mediated antitumor response (138,(189)(190)(191)(192).…”

Section: Combination Therapy With Cpg-odns and Immune Checkpoint Inhimentioning

confidence: 99%

“…B cells generate a humoral response by secreting antibodies specific to tumor antigens. T-cells are classified into two major subsets: CD4 + helper Tcells release immunomodulatory cytokines, and CD8 + cytolytic T-cells act as effector cells to directly lyse tumor cells during the adaptive antitumor immune response (28)(29)(30)(31).…”

Section: Introductionmentioning

confidence: 99%

“…Thus, the immune system employs coordinated innate immunity and adaptive immunity to fight tumors. This observation provides the rationale for boosting the efficacy (including strength and precision) of an adaptive antitumor immunotherapy such as checkpoint blockade by targeting innate immune cells to activate of the adjuvant response or priming effect (28)(29)(30)(31). TLRs are broadly expressed in immune cells for the detection of microbial pathogens to initiate host responses to infection (32)(33)(34).…”

Section: Introductionmentioning

confidence: 99%

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Adjuvant Effect of Toll-Like Receptor 9 Activation on Cancer Immunotherapy Using Checkpoint Blockade

et al. 2020

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Immunotherapy using checkpoint blockade has revolutionized cancer treatment, improving patient survival and quality of life. Nevertheless, the clinical outcomes of such immunotherapy are highly heterogeneous between patients. Depending on the cancer type, the patient response rates to this immunotherapy are limited to 20-30%. Based on the mechanism underlying the antitumor immune response, new therapeutic strategies have been designed with the aim of increasing the effectiveness and specificity of the antitumor immune response elicited by checkpoint blockade agents. The activation of toll-like receptor 9 (TLR9) by its synthetic agonists induces the antitumor response within the innate immunity arm, generating adjuvant effects and priming the adaptive immune response elicited by checkpoint blockade during the effector phase of tumor-cell killing. This review first describes the underlying mechanisms of action and current status of monotherapy using TLR9 agonists and immune checkpoint inhibitors for cancer immunotherapy. The rationale for combining these two agents is discussed, and evidence indicating the current status of such combination therapy as a novel cancer treatment strategy is presented.

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Section: Combination Therapy With Cpg-odns and Immune Checkpoint Inhimentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Adjuvant Effect of Toll-Like Receptor 9 Activation on Cancer Immunotherapy Using Checkpoint Blockade

et al. 2020

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“…The ligation of CD40 on macrophages, dendritic cells, and B cells leads to activation of these cells, enhances antigen presentation, and induces an effective T cell anti-tumor response [17][18][19]. Previous research publications, leading to the current components of MBTA therapy, have been published here [12,20,21] and summarized in this review [22].…”

Section: Introductionmentioning

confidence: 98%

Identification of Immune Cell Infiltration in Murine Pheochromocytoma during Combined Mannan-BAM, TLR Ligand, and Anti-CD40 Antibody-Based Immunotherapy

Uher

Huynh

Zhu

et al. 2021

Cancers

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Immunotherapy has become an essential component in cancer treatment. However, the majority of solid metastatic cancers, such as pheochromocytoma, are resistant to this approach. Therefore, understanding immune cell composition in primary and distant metastatic tumors is important for therapeutic intervention and diagnostics. Combined mannan-BAM, TLR ligand, and anti-CD40 antibody-based intratumoral immunotherapy (MBTA therapy) previously resulted in the complete eradication of murine subcutaneous pheochromocytoma and demonstrated a systemic antitumor immune response in a metastatic model. Here, we further evaluated this systemic effect using a bilateral pheochromocytoma model, performing MBTA therapy through injection into the primary tumor and using distant (non-injected) tumors to monitor size changes and detailed immune cell infiltration. MBTA therapy suppressed the growth of not only injected but also distal tumors and prolonged MBTA-treated mice survival. Our flow cytometry analysis showed that MBTA therapy led to increased recruitment of innate and adaptive immune cells in both tumors and the spleen. Moreover, adoptive CD4+ T cell transfer from successfully MBTA-treated mice (i.e., subcutaneous pheochromocytoma) demonstrates the importance of these cells in long-term immunological memory. In summary, this study unravels further details on the systemic effect of MBTA therapy and its use for tumor and metastasis reduction or even elimination.

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“…Listeria is rich in mechanisms to stimulate innate immunity directly in tumors 36 . Direct intratumoral injection of bacteria or bacterial products may have underlied the success of William Coley's early therapies 37 . Recent preclinical studies as well as clinical trials have demonstrated the feasibility and efficacy of direct intratumoral injection of immune adjuvants naturally generated by Listeria and other bacterial species that can activate host cell pattern recognition receptors (PRRs) and stimulate the innate immune response against tumors [38][39][40] .…”

Section: Introductionmentioning

confidence: 99%

Cellular mechanisms underlying beneficial versus detrimental effects of bacterial antitumor immunotherapy

Castillo,

Fernandez,

Campbell

et al. 2024

Preprint

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SummaryListeria monocytogenesengineered to express tumor antigens as a cancer vaccine has yielded mixed results. Here, we utilized an attenuated strain ofListeria(ΔactA, Lm) that does not express tumor antigen to explore the immunological response toListeriaitself in the context of intravenous (IV), intratumoral (IT), or a combination of IV+IT administration into tumor-bearing mice. Unexpectedly, we found thatLmpersisted in tumors of immune competent mice, regardless of the administration route. While ITLmalone led to the recruitment of immunosuppressive immune cells that promoted tumor growth, IVLmfollowed by ITLmcontrolled tumor growth. IVLmvaccination generated a pool of anti-Lmcytotoxic CD8 T cells that killedLm-infected non-tumor cells to control tumor growth. Our findings reveal a differential impact of ITLmadministration on tumor progression that depends on the presence of anti-LmCD8 T cells, rather than antitumor CD8 T cells, for antitumor therapeutic efficacy.

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Coley's immunotherapy revived: Innate immunity as a link in priming cancer cells for an attack by adaptive immunity

Cited by 13 publications

References 69 publications

Adjuvant Effect of Toll-Like Receptor 9 Activation on Cancer Immunotherapy Using Checkpoint Blockade

Adjuvant Effect of Toll-Like Receptor 9 Activation on Cancer Immunotherapy Using Checkpoint Blockade

Identification of Immune Cell Infiltration in Murine Pheochromocytoma during Combined Mannan-BAM, TLR Ligand, and Anti-CD40 Antibody-Based Immunotherapy

Cellular mechanisms underlying beneficial versus detrimental effects of bacterial antitumor immunotherapy

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