New Checkpoint Inhibitors on the Road: Targeting TIM-3 in Solid Tumors

Morais, Ana Luiza Gomes de; Cerdá, Sara Sirvent; Miguel, Maria J. de

doi:10.1007/s11912-022-01218-y

Cited by 36 publications

(29 citation statements)

References 66 publications

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“…TIM-3 is a receptor that has a significant role in the immune checkpoint. TIM-3 is also termed hepatitis A virus cellular receptor 2 (HAVCR2) or CD366 [ 10 , 12 ]. This protein consists of a C-terminal cytoplasmic tail, a single transmembrane domain signal peptides, a mucinlike domain and an extracellular N-terminal variable immunoglobulin (IgV) domain [ 13 ].…”

Section: Tim-3mentioning

confidence: 99%

“…TIM-3 during HCV infection can inhibit the maturation of dendritic cells [ 15 ]. In both HCV and HIV (human immunodeficiency virus) infection, TIM-3 expression on CD4 + and CD8 + cells is associated with T-cell exhaustion [ 10 ]. In the autoimmune disease course, it is worth highlighting the correlation of TIM-3 to the disease progression.…”

Section: Tim-3mentioning

confidence: 99%

“…This reduces drug bioavailability and causes local immune system suppression within the tumor [ 8 , 9 ]. Chronic antigen stimulation, known as T cell exhaustion, causes T cell dysfunction and is one of the key aspects of the lack of a sustained immune response to cancer [ 10 ]. The exhausted, dysfunctional state is not necessarily permanent.…”

Section: Introductionmentioning

confidence: 99%

“…Clinical anticancer strategies used in immunotherapy include therapies based on the inhibition of programmed cell death protein 1 (PD-1), its ligand (PD-L1) or cytotoxic T-lymphocyte antigen-4 (CTLA-4). Despite encouraging results, a large proportion of cancer patients are resistant to these therapies or eventually develop resistance [ 10 ]. The introduction of innovative drugs based on immunological target points may offer hope not only in treating cancer recurrence and extending progression-free survival but also in trying to cure patients completely.…”

Section: Introductionmentioning

confidence: 99%

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The Role of TIM-3 and LAG-3 in the Microenvironment and Immunotherapy of Ovarian Cancer

2022

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Ovarian cancer has the highest mortality rate among gynecologic malignancies. The main treatment options are surgical removal of the tumor and chemotherapy. Cancer treatment has been revolutionized by immunotherapy, which has developed explosively over the past two decades. Clinical anticancer strategies used in immunotherapy include therapies based on the inhibition of PD-1, PD-L1 or CTLA-4. Despite encouraging results, a large proportion of cancer patients are resistant to these therapies or eventually develop resistance. It is important to perform research that will focus on immunotherapy based on other immune checkpoint inhibitors. The aim of the review was to analyze studies considering the expression of TIM-3 and LAG-3 in the ovarian cancer microenvironment and considering immunotherapy for ovarian cancer that includes antibodies directed against TIM-3 and LAG-3. As the data showed, the expression of the described immune checkpoints was shown in different ways. Higher TIM-3 expression was associated with a more advanced tumor stage. Both TIM-3 and LAG-3 were co-expressed with PD-1 in a large proportion of studies. The effect of LAG-3 expression on progression-free survival and/or overall survival is inconclusive and certainly requires further study. Co-expression of immune checkpoints prompts combination therapies using anti-LAG-3 or anti-TIM-3. Research on immune checkpoints, especially TIM-3 and LAG-3, should be further developed.

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Section: Tim-3mentioning

confidence: 99%

Section: Tim-3mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Role of TIM-3 and LAG-3 in the Microenvironment and Immunotherapy of Ovarian Cancer

2022

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“…Targeting TIM-3 is another strategy based on T-cell immunotherapy. TIM-3 is an important tumor immune checkpoint expressed on a variety of immune cells including effector T cells, monocytes, NK, and DCs ( 75 , 76 ), which can inhibit innate and T-cell immune response ( 77 , 78 ), participate in immune escape ( 79 ), and promote immune tolerance ( 80 ). Blocking TIM-3 pathway can positively regulate innate and adaptive immunity, alleviate T-cell depletion, and increase the secretion of interferon-γ (IFN-γ) by NK and T cells ( 75 , 81 ).…”

Section: Tim-3mentioning

confidence: 99%

Therapeutic strategies for gastric cancer targeting immune cells: Future directions

et al. 2022

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Gastric cancer (GC) is a malignancy with a high incidence and mortality, and the emergence of immunotherapy has brought survival benefits to GC patients. Compared with traditional therapy, immunotherapy has the advantages of durable response, long-term survival benefits, and lower toxicity. Therefore, targeted immune cells are the most promising therapeutic strategy in the field of oncology. In this review, we introduce the role and significance of each immune cell in the tumor microenvironment of GC and summarize the current landscape of immunotherapy in GC, which includes immune checkpoint inhibitors, adoptive cell therapy (ACT), dendritic cell (DC) vaccines, reduction of M2 tumor-associated macrophages (M2 TAMs), N2 tumor-associated neutrophils (N2 TANs), myeloid-derived suppressor cells (MDSCs), effector regulatory T cells (eTregs), and regulatory B cells (Bregs) in the tumor microenvironment and reprogram TAMs and TANs into tumor killer cells. The most widely used immunotherapy strategies are the immune checkpoint inhibitor programmed cell death 1/programmed death-ligand 1 (PD-1/PD-L1) antibody, cytotoxic T lymphocyte–associated protein 4 (CTLA-4) antibody, and chimeric antigen receptor T (CAR-T) in ACT, and these therapeutic strategies have significant anti-tumor efficacy in solid tumors and hematological tumors. Targeting other immune cells provides a new direction for the immunotherapy of GC despite the relatively weak clinical data, which have been confirmed to restore or enhance anti-tumor immune function in preclinical studies and some treatment strategies have entered the clinical trial stage, and it is expected that more and more effective immune cell–based therapeutic methods will be developed and applied.

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Checkpoint blockade meets gene therapy: Opportunities to improve response and reduce toxicity

Silva-Pilipich

Covo-Vergara

Vanrell

et al. 2023

Viral Vectors in Cancer Immunotherapy

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New Checkpoint Inhibitors on the Road: Targeting TIM-3 in Solid Tumors

Cited by 36 publications

References 66 publications

The Role of TIM-3 and LAG-3 in the Microenvironment and Immunotherapy of Ovarian Cancer

The Role of TIM-3 and LAG-3 in the Microenvironment and Immunotherapy of Ovarian Cancer

Therapeutic strategies for gastric cancer targeting immune cells: Future directions

Checkpoint blockade meets gene therapy: Opportunities to improve response and reduce toxicity

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