Immunomodulation by targeted anticancer agents

Petroni, Giulia; Buqué, Aitziber; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

doi:10.1016/j.ccell.2020.11.009

Cited by 163 publications

(107 citation statements)

References 311 publications

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“…Herein, T cell infiltration was rarely observed in both the tumor models, however, the infiltration was improved to the greatest extent after the administration of the combination treatment. It has been reported that Foretinib promote apoptosis, induce programmed cell death and inhibit angiogenesis by targeted multiple tyrosine kinases, these could release antigens and jumpstart the so-called cancer-immunity cycle, secrete chemoattractant to enhancing T cells infiltration (Huynh et al, 2012;Chen et al, 2017;Kogata et al, 2018;Liu et al, 2019;Hack et al, 2020;Petroni et al, 2021). And in our study, the genes associated with T cell recruitment were enriched within the tumor after the combination treatment, this implies there were more T cells infiltration in tumor.…”

Section: Discussionsupporting

confidence: 57%

Combination Foretinib and Anti-PD-1 Antibody Immunotherapy for Colorectal Carcinoma

Peng

Zhao

et al. 2021

Front. Cell Dev. Biol.

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Immune checkpoint inhibitors have achieved unprecedented success in cancer immunotherapy. However, the overall response rate to immune checkpoint inhibitor therapy for many cancers is only between 20 and 40%, and even less for colorectal cancer (CRC) patients. Thus, there is an urgent need to develop an efficient immunotherapeutic strategy for CRC. Here, we developed a novel CRC combination therapy consisting of a multiple receptor tyrosine kinase inhibitor (Foretinib) and anti-PD-1 antibody. The combination therapy significantly inhibited tumor growth in mice, led to improved tumor regression without relapse (83% for CT26 tumors and 50% for MC38 tumors) and prolonged overall survival. Mechanistically, Foretinib caused increased levels of PD-L1 via activating the JAK2-STAT1 pathway, which could improve the effectiveness of the immune checkpoint inhibitor. Moreover, the combination therapy remodeled the tumor microenvironment and enhanced anti-tumor immunity by further increasing the infiltration and improving the function of T cells, decreasing the percentage of tumor-associated macrophages (TAMs) and inhibiting their polarization toward the M2 phenotype. Furthermore, the combination therapy inhibited the metastasis of CT26-Luc tumors to the lung in BALB/c mouse by reducing proportions of regulatory T-cells, TAMs and M2 phenotype TAMs in their lungs. This study suggests that a novel combination therapy utilizing both Foretinib and anti-PD-1 antibody could be an effective combination strategy for CRC immunotherapy.

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Section: Discussionsupporting

confidence: 57%

Combination Foretinib and Anti-PD-1 Antibody Immunotherapy for Colorectal Carcinoma

Peng

Zhao

et al. 2021

Front. Cell Dev. Biol.

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“…It is reported antibody therapy mediated immune stimulation and PD-L1 blockers, can be exploited to magnify the efficacy of HER2-targeting mAbs along with the elicitation of robust anticancer immunity. 24 Subsequent in vitro and in vivo experiments are needed to confirm the probable synergism between these two agents.…”

Section: Discussionmentioning

confidence: 99%

Durable Clinical Response to Immune and Targeted Therapies in an Elderly Man with Synchronous Gastric (HER2+) and Bladder Cancers: Case Report and Literature Review

Tian

Zhu

Zhang

2021

OTT

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Synchronous occurrences of gastric cancer positive for human epidermal growth factor receptor 2 (HER2+) and bladder cancer are rarely encountered in clinical practice. When and how to effectively treat both tumors, without compounding adverse effects, must be addressed. Herein, we describe an elderly man who presented with both gastric cancer (HER2+) and bladder cancer. Due to enlarged and fused lymph nodal metastasis, he was illsuited for stomach resection. After transurethral resection of the bladder tumor, we administered both chemotherapy and the targeted agent trastuzumab. Gastric cancer showed partial response however bladder cancer recurred following two cycles of this regimen, the adverse effects were prohibitive, prompting refusal of further chemotherapy and radiotherapy. He then received the immune checkpoint inhibitor (ICI) nivolumab and trastuzumab in combination. This particular regimen successfully controlled both cancers and substantially improved the patient's quality of life. Its long-term use did not intensify adverse reactions, enabling a progression-free survival of 21 months to date. We have also reviewed other published clinical strategies applied in rare instances of multiple primary malignancies as a reference for treating such patients.

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“…DNA repair and angiogenesis pathways have provided effective treatment options for patients with different types of malignant tumors. Several studies have shown that these pathways also display immunomodulatory effects on systemic and intratumoral antitumor immune responses; thus, suggesting that the combination of molecular targeted therapy and ICI treatment might elicit synergistic antitumor effects and can be explored in HIS mice for producing synergistic antitumor effects (64).…”

Section: Immunotherapy Combined With Targeted Drug Therapymentioning

confidence: 99%

Strategies for the Construction of Mouse Models With Humanized Immune System and Evaluation of Tumor Immune Checkpoint Inhibitor Therapy

et al. 2021

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Immunotherapy has been used as a first-line treatment for a variety of advanced tumors, allowing remarkable progress to be made in cancer treatment. Nonetheless, only a small number of patients can benefit from immune checkpoint inhibitor monotherapy. To improve the effect of immunotherapy, the underlying mechanism of combination therapy was investigated in the context of an intact human tumor immune microenvironment using mice with a human immune system (HIS) bearing human tumors. Herein, we summarize and discuss strategies for the development and use of HIS mice models in tumor immunotherapies. Most importantly, this review proposes a method of t11umor identification and classification in HIS mice based on the tumor-infiltrating lymphocytes and PD-L1 expression, and according to this classification, we propose different combination treatment strategies that can be utilized to enhance the effect of immunotherapy. Thus, we provide effective experimental schemes for tumor immunotherapy in HIS mice models.

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Immunomodulation by targeted anticancer agents

Cited by 163 publications

References 311 publications

Combination Foretinib and Anti-PD-1 Antibody Immunotherapy for Colorectal Carcinoma

Combination Foretinib and Anti-PD-1 Antibody Immunotherapy for Colorectal Carcinoma

Durable Clinical Response to Immune and Targeted Therapies in an Elderly Man with Synchronous Gastric (HER2+) and Bladder Cancers: Case Report and Literature Review

Strategies for the Construction of Mouse Models With Humanized Immune System and Evaluation of Tumor Immune Checkpoint Inhibitor Therapy

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