Current Challenges in Cancer Immunotherapy: Multimodal Approaches to Improve Efficacy and Patient Response Rates

Sambi, Manpreet; Bagheri, Leila; Szewczuk, Myron R.

doi:10.1155/2019/4508794

Cited by 230 publications

(179 citation statements)

References 60 publications

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“…CLTA-4 is a receptor that is expressed on the surface of T cells and inactivates T cell activity by competing against CD28 to bind to the two T cell activation antigens CD80 and CD86, found on the surface of antigen-presenting cells (APC). In addition, the PD-1 receptor is also found on T cells, where, upon binding to the ligand PD-L1, induces a conformational change to an inactive and dysfunctional state [35]. As such, by targeting these two checkpoint pathways, the baseline of T cell activity can be restored to reactivate tumour immunosurveillance ( Figure 2).…”

Section: Immune Checkpoint Inhibitorsmentioning

confidence: 99%

Myeloid-Derived Suppressor Cells as a Therapeutic Target for Cancer

Law

Valdés-Mora

Gallego‐Ortega

2020

Cells

330

272

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The emergence of immunotherapy has been an astounding breakthrough in cancer treatments. In particular, immune checkpoint inhibitors, targeting PD-1 and CTLA-4, have shown remarkable therapeutic outcomes. However, response rates from immunotherapy have been reported to be varied, with some having pronounced success and others with minimal to no clinical benefit. An important aspect associated with this discrepancy in patient response is the immune-suppressive effects elicited by the tumour microenvironment (TME). Immune suppression plays a pivotal role in regulating cancer progression, metastasis, and reducing immunotherapy success. Most notably, myeloid-derived suppressor cells (MDSC), a heterogeneous population of immature myeloid cells, have potent mechanisms to inhibit T-cell and NK-cell activity to promote tumour growth, development of the pre-metastatic niche, and contribute to resistance to immunotherapy. Accumulating research indicates that MDSC can be a therapeutic target to alleviate their pro-tumourigenic functions and immunosuppressive activities to bolster the efficacy of checkpoint inhibitors. In this review, we provide an overview of the general immunotherapeutic approaches and discuss the characterisation, expansion, and activities of MDSCs with the current treatments used to target them either as a single therapeutic target or synergistically in combination with immunotherapy.

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Section: Immune Checkpoint Inhibitorsmentioning

confidence: 99%

Myeloid-Derived Suppressor Cells as a Therapeutic Target for Cancer

Law

Valdés-Mora

Gallego‐Ortega

2020

Cells

330

272

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“…Preclinical and clinical efforts are pushing forward with combination ICI therapy as well as ushering in different approaches to harness the immune system to extend immunotherapy efficacy to more patients, including vaccines and viral therapy, adoptive cell transfer, and cytokine treatment (12,28). Challenges with improving efficacy include overcoming immunosuppression activity by the tumor microenvironment, unmasking pre-existing immune cell activity, and the ability to stimulate de novo immunogenicity (29). In recent years, antibodies and small molecular inhibitors against CD73 have made their way into clinical trials as an attractive target for restoring antitumor immunity (30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44).…”

Section: Introductionmentioning

confidence: 99%

CD73's Potential as an Immunotherapy Target in Gastrointestinal Cancers

et al. 2020

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CD73, a cell surface 5 ′ nucleotidase that generates adenosine, has emerged as an attractive therapeutic target for reprogramming cancer cells and the tumor microenvironment to dampen antitumor immune cell evasion. Decades of studies have paved the way for these findings, starting with the discovery of adenosine signaling, particularly adenosine A2A receptor (A2AR) signaling, as a potent suppressor of tissue-devastating immune cell responses, and evolving with studies focusing on CD73 in breast cancer, melanoma, and non-small cell lung cancer. Gastrointestinal (GI) cancers are a major cause of cancer-related deaths. Evidence is mounting that shows promise for improving patient outcomes through incorporation of immunomodulatory strategies as single agents or in combination with current treatment options. Recently, several immune checkpoint inhibitors received FDA approval for use in GI cancers; however, clinical benefit is limited. Investigating molecular mechanisms promoting immunosuppression, such as CD73, in GI cancers can aid in current efforts to extend the efficacy of immunotherapy to more patients. In this review, we discuss current clinical and basic research studies on CD73 in GI cancers, including gastric, liver, pancreatic, and colorectal cancer, with special focus on the potential of CD73 as an immunotherapy target in these cancers. We also present a summary of current clinical studies targeting CD73 and/or A2AR and combination of these therapies with immune checkpoint inhibitors.

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“…Another challenge remains is the wide variety of atypical clinical response patterns that can be seen across patients with what looks like to be the same type of disease. [61][62][63] Efficacy of immunotherapy varies widely from one patient to the other, even within the same subtype.…”

Section: Immunotherapy Challengesmentioning

confidence: 99%

<p>Immunotherapy for the Treatment of Breast Cancer: Emerging New Data</p>

Mina

Lim

Bahadur

et al. 2020

BCTT

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Breast cancer is the most common type of cancer affecting women in the United States. Triple-negative breast cancer remains the most aggressive molecular subtype secondary to a lack of therapeutic targets. The search for a target has led us to investigate immunotherapeutic agents. Immunotherapy has recently demonstrated significant breakthroughs in various types of cancers that are refractory to traditional therapies including melanoma and Non-Small Cell Lung Cancer (NSCLC). Breast cancer however remains one of the tumors that was initially least investigated because of being considered to have a low immunogenic potential and a low mutational load. Over the past few years, antiPD1/PDL1 drugs have started to make progress in the triple-negative subtype with more promising outcomes. In this report, we review the treatment of triple-negative breast cancer and specifically shed light on advances in immunotherapy and newly approved drugs in this challenging disease.

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Current Challenges in Cancer Immunotherapy: Multimodal Approaches to Improve Efficacy and Patient Response Rates

Cited by 230 publications

References 60 publications

Myeloid-Derived Suppressor Cells as a Therapeutic Target for Cancer

Myeloid-Derived Suppressor Cells as a Therapeutic Target for Cancer

CD73's Potential as an Immunotherapy Target in Gastrointestinal Cancers

<p>Immunotherapy for the Treatment of Breast Cancer: Emerging New Data</p>

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