Role of OX40 and its ligand as costimulatory modulators in cancer immunotherapy

Aliya I Sani; Zil-e-Rubab; Shumaila Usman; Syed Zaryab Ahmed; Mervyn Hosein; Aliya I Sani; Zil-e-Rubab; Shumaila Usman; Syed Zaryab Ahmed; Mervyn Hosein

doi:10.3934/molsci.2021012

AIMS Molecular Science

2021, Volume 8, Issue 3: 161-173. doi: 10.3934/molsci.2021012

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Review

Role of OX40 and its ligand as costimulatory modulators in cancer immunotherapy

1.
Department of Biochemistry, Ziauddin University, Karachi, Pakistan
2.
Department of Research, Ziauddin University, Karachi, Pakistan
3.
Department of Dentistry, Ziauddin University, Karachi, Pakistan

Received: 09 March 2021 Accepted: 30 June 2021 Published: 05 July 2021

Body's defence mechanism has ability to combat tumour cells but tumour cells can circumvent immune system in order to flourish. Therefore, current research focuses on reinvigorating immune system to combat against extensive range of human malignancies through immunotherapy. Recently, immuno-therapy has demonstrated beneficial outcomes in cancers treatment but the main drawbacks are primary and acquired resistance to the therapeutic agents and immune-related toxicities. Therefore, novel immune therapies are direly required. Co-stimulatory molecules such as TNF Receptor Superfamily Member 4 (OX40, CD134) and its ligand TNF Superfamily Member 4 (CD252, OX40L) are expressed on different immune cells. The mutual interaction between OX40 and its ligand (OX40/OX40L) decreases the functional capacity of immunosuppression offered by regulatory T cells (Tregs) and induces the proliferation of T cells against specific antigen enhancing the immune response. Many clinical trials are focusing on OX40/OX40L therapeutic agents to find out whether they have therapeutic effect on cancer treatment. The initial phase trials result of OX40 and its ligands focusing therapeutic agents are encouraging but still not sufficient. This review will concentrate on the cellular and molecular pathways of OX40-mediated T-cell co-stimulation, the expression of OX40 and OX40L in tumours, the implications of their interactions and their under-or over-expression patterns, with particular focus on the function of OX40 in tumours of different origins. Finally, we discuss results of clinical trials of OX40 and OX40L directed pharmacotherapy and the lacunae that need to be filled.
- OX40,
- OX40 ligand,
- T-cells,
- immunotherapy
Citation: Aliya I Sani, Zil-e-Rubab, Shumaila Usman, Syed Zaryab Ahmed, Mervyn Hosein. Role of OX40 and its ligand as costimulatory modulators in cancer immunotherapy[J]. AIMS Molecular Science, 2021, 8(3): 161-173. doi: 10.3934/molsci.2021012

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Abstract

Body's defence mechanism has ability to combat tumour cells but tumour cells can circumvent immune system in order to flourish. Therefore, current research focuses on reinvigorating immune system to combat against extensive range of human malignancies through immunotherapy. Recently, immuno-therapy has demonstrated beneficial outcomes in cancers treatment but the main drawbacks are primary and acquired resistance to the therapeutic agents and immune-related toxicities. Therefore, novel immune therapies are direly required. Co-stimulatory molecules such as TNF Receptor Superfamily Member 4 (OX40, CD134) and its ligand TNF Superfamily Member 4 (CD252, OX40L) are expressed on different immune cells. The mutual interaction between OX40 and its ligand (OX40/OX40L) decreases the functional capacity of immunosuppression offered by regulatory T cells (Tregs) and induces the proliferation of T cells against specific antigen enhancing the immune response. Many clinical trials are focusing on OX40/OX40L therapeutic agents to find out whether they have therapeutic effect on cancer treatment. The initial phase trials result of OX40 and its ligands focusing therapeutic agents are encouraging but still not sufficient. This review will concentrate on the cellular and molecular pathways of OX40-mediated T-cell co-stimulation, the expression of OX40 and OX40L in tumours, the implications of their interactions and their under-or over-expression patterns, with particular focus on the function of OX40 in tumours of different origins. Finally, we discuss results of clinical trials of OX40 and OX40L directed pharmacotherapy and the lacunae that need to be filled.

Abbreviations

APCs

antigen presenting cells

CTLA-4

cytotoxic T-lymphocyte-associated protein 4

FOXp3

forkhead box P3

HCC

Hepatocellular carcinoma

MHC

major histocompatibility complex

Natural Killer cell

NSLC

Non-small cell lung carcinoma

OSCC

Oral squamous cell carcinoma

OX40

Tumour necrosis factor receptor superfamily member 4

OX40L

Tumour necrosis factor superfamily member 4 ligand

TCR

T cell receptor

Tregs

Regulatory T cells

Conflict of interest

All authors declare no conflict of interest in this paper.

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