Short Communication - Journal of Cancer Immunology & Therapy (2023) Volume 6, Issue 3

A brief comment on immune escape pathways in cancer and overcoming resistance.

Grady Ozalp^*

Department of General, Visceral, and Transplantation Surgery, University Hospital, LMU Munich, Munich, Germany

*Corresponding Author:

Grady Ozalp
Department of General, Visceral, and Transplantation Surgery
University Hospital, LMU Munich
Munich, Germany
E-mail:ozalp.gr@gmail.com

Received:19-May-2023,Manuscript No. AAJCIT-23-102151; Editor assigned: 30-May-2023, PreQC No. AAJCIT-23-102151(PQ); Reviewed:06-Jun-2023, QC No. AAJCIT-23-102151; Revised:12-Jun-2023, Manuscript No. AAJCIT-23-102151(R); Published:19-Jun-2023, DOI: 10.35841/aajcit- 6.3.151

Citation: Ozalp G.A brief comment on immune escape pathways in cancer and overcoming resistance. J Cancer Immunol Ther. 2023;6(3):151

Abstract

Introduction

The immune system plays a crucial role in recognizing and eliminating abnormal cells, including cancer cells. However, cancer has the ability to evade immune surveillance through various mechanisms, leading to immune escape. Immune escape hampers the effectiveness of immunotherapies, such as immune checkpoint inhibitors, which have revolutionized cancer treatment in recent years. Overcoming immune resistance is a key challenge in the field of cancer immunotherapy. This article provides a concise overview of the mechanisms behind immune escape in cancer and explores the current strategies employed to overcome resistance. Immune escape is a phenomenon in cancer where tumor cells evade the immune system's ability to recognize and eliminate them, leading to treatment resistance. This short note provides an overview of the mechanisms underlying immune escape in cancer and highlights strategies employed to overcome resistance. Mechanisms of immune escape include tumor antigen heterogeneity, activation of immune checkpoints, immunosuppressive tumor microenvironment, and loss of tumor antigen presentation. To overcome resistance, combination immunotherapies, novel immune checkpoint blockade, targeting tumor heterogeneity, modulating the tumor microenvironment, combination with conventional therapies, and targeting metabolic pathways are being explored. Understanding and addressing immune escape mechanisms are crucial for the development of effective cancer immunotherapies and improved patient outcomes[1].

Mechanisms of immune escape

Tumor Antigen Heterogeneity

Cancer cells exhibit significant heterogeneity, resulting in the presence of diverse tumor antigens. This heterogeneity enables the emergence of antigen-negative variants, allowing cancer cells to evade immune recognition. Additionally, tumors can downregulate antigen presentation molecules, such as major histocompatibility complex (MHC) molecules, further compromising immune recognition.

Immune checkpoint activation

Immune checkpoint molecules, such as programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), serve as inhibitory signals that suppress immune responses. Tumor cells can upregulate these checkpoints, leading to T cell exhaustion and impaired anti-tumor immunity. This mechanism enables cancer cells to evade immune destruction[2].

Immunosuppressive Tumor Microenvironment (TME)

The TME comprises a complex network of immune cells, stromal cells, and signaling molecules. Within the TME, tumor-associated immune cells, such as regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs), exert immunosuppressive effects. Tregs inhibit T cell activation, while MDSCs suppress the function of effector immune cells. Additionally, the TME can be enriched with anti-inflammatory cytokines and metabolites that dampen immune responses, further promoting immune escape[3].

Loss of tumor antigen presentation

Cancer cells can downregulate or mutate components involved in antigen presentation, including MHC molecules and antigen processing machinery. This loss of antigen presentation restricts the ability of immune cells to recognize and eliminate cancer cells effectively.

Combination immunotherapies

Combining different immunotherapeutic approaches has shown promise in overcoming immune resistance. For instance, combining immune checkpoint inhibitors targeting PD-L1 or CTLA-4 with other immunotherapies, such as chimeric antigen receptor (CAR) T cell therapy or therapeutic vaccines, has demonstrated enhanced anti-tumor responses. Combination therapies have the potential to target multiple immune escape mechanisms simultaneously, improving treatment efficacy[4].

Novel immune checkpoint blockade

Expanding the repertoire of immune checkpoint inhibitors beyond PD-L1 and CTLA-4 holds potential for overcoming resistance. Recent studies have identified additional inhibitory checkpoints, such as T cell immunoglobulin and mucin domain-containing molecule 3 (TIM-3) and lymphocyte-activation gene 3 (LAG-3). Targeting these checkpoints in combination with existing therapies could enhance the anti-tumor immune response.

Overcoming tumor heterogeneity

Developing strategies to target the heterogeneity of tumor antigens is crucial for effective immunotherapy. Personalized neoantigen vaccines can be designed to elicit immune responses against specific antigens present in individual patients' tumors. Additionally, targeting shared tumor-associated antigens or cancer-testis antigens that are expressed in multiple tumor types could broaden the scope of immunotherapeutic approaches.

Modulating the tumor microenvironment

Efforts to modify the immunosuppressive TME are underway. This includes inhibiting immunosuppressive cells, such as Tregs and MDSCs, or reprogramming them to become pro-inflammatory cells. Additionally, strategies involving the use of cytokines, such as interleukin-12 (IL-12) or interferon-gamma (IFN-γ), aim to shift the TME towards a pro-inflammatory state, enhancing anti-tumor immune responses.

Combination with conventional therapies

Combining immunotherapies with traditional treatments, such as chemotherapy or radiation therapy, has shown promise in enhancing immune responses. Conventional therapies can induce immunogenic cell death, releasing tumor antigens and promoting immune activation. Moreover, they can modify the TME, making it more receptive to immune-mediated killing.

Targeting metabolic pathways

Altered metabolism is a hallmark of cancer, and targeting metabolic pathways can potentially overcome immune resistance. For instance, inhibiting indoleamine 2,3-dioxygenase (IDO), an enzyme involved in tryptophan metabolism, has been shown to enhance anti-tumor immune responses. Similarly, targeting adenosine signaling pathways or metabolic checkpoints, such as mTOR, may improve the efficacy of immunotherapies[5].

Conclusion

Immune escape is a major hurdle in cancer immunotherapy, limiting the effectiveness of current treatments. However, significant progress has been made in understanding the mechanisms of immune resistance, leading to the development of novel strategies to overcome it. Combination therapies, targeting multiple immune escape mechanisms, personalized vaccines, and modulation of the tumor microenvironment show promise in enhancing anti-tumor immune responses. Continued research and clinical trials are essential for the successful translation of these strategies into clinical practice, ultimately improving patient outcomes in the battle against cancer.

References

1. Hamid O, Robert C, Daud A, et al.Safety and tumor responses with lambrolizumab (anti–PD-1) in melanoma.N Eng J Med. 2013;369(2):134-44.

Indexed at, Google Scholar, Cross Ref

2. Thomas L.On immunosurveillance in human cancer.Yale J Biol Med. 1982;55(3-4):329.

Indexed at, Google Scholar

3. Ferrone C, Dranoff G.. Dual roles for immunity in gastrointestinal cancers.J Clin Oncol. 2010;28(26):4045.

Indexed at, Google Scholar, Cross Ref

4. Johnsen AK, Templeton DJ, Sy MS, et al.Deficiency of transporter for antigen presentation (TAP) in tumor cells allows evasion of immune surveillance and increases tumorigenesis.J Immunol. 1999;163(8):4224-31.

Indexed at, Google Scholar, Cross Ref

5. Kitamura H, Torigoe T, Honma I, et al.Effect of human leukocyte antigen class I expression of tumor cells on outcome of intravesical instillation of bacillus calmette-guerin immunotherapy for bladder cancer.Clin Cancer Res. 2006;12(15):4641-4.

Indexed at, Google Scholar, Cross Ref