The Complex Relationship between Tumors and Immune Responses

Barchetti Mertens^*
*Correspondence: Barchetti Mertens, Department of Biotechnology and Biosciences, University of Milano-Bicocca, 20126 Milan, Italy, Email:

Introduction

The immune system serves as the bodyâ??s surveillance mechanism, capable of detecting and destroying abnormal cells to maintain physiological homeostasis. However, tumors-arising from host tissues-exploit this intricate system to evade detection, suppress immune responses and support their own growth and metastasis. The relationship between tumors and immune responses is multifaceted, encompassing both protective and promotive roles. While immunosurveillance eliminates nascent cancer cells, certain immune cells and signaling molecules can paradoxically promote tumor progression [1].

Understanding the complex crosstalk between tumors and the immune system has led to a new era in oncology. Immune checkpoint inhibitors, adoptive T-cell therapies and cancer vaccines have emerged as powerful tools in the therapeutic arsenal. Yet, these treatments are not universally effective, reflecting the profound heterogeneity of tumor-immune interactions. This article explores the cellular and molecular dynamics that define the tumor-immune relationship, the mechanisms tumors use to subvert immune control and how this knowledge is shaping the development of novel cancer immunotherapies [2].

Description

Coined by Dunn, Old and Schreiber, immunoediting describes the dual role of the immune system in controlling and shaping tumor development. Immune cells recognize and destroy transformed cells. Surviving tumor variants persist in a dormant state. Tumor cells evade immune detection and grow progressively. Recognize tumor-associated antigens and kill tumor cells via perforin and granzyme release. Target cells lacking MHC class I molecules. Present tumor antigens to naïve T cells to initiate adaptive responses. Can have tumoricidal M1 or tumor-promoting M2 phenotypes. Tumors have evolved sophisticated strategies to evade immune destruction, often reshaping the tumor microenvironment (TME) to suppress anti-tumor responses. Tumor-expressed PD-L1 binds to PD-1 on T cells, inhibiting their cytotoxic function. Competes with CD28 for binding B7 on APCs, leading to reduced T-cell activation. Suppress effector T cell activity and promote immune tolerance within the TME. Immune recognition hinges on the presentation of tumor antigens. Mutated proteins unique to tumor cells (e.g., neoantigens from nonsynonymous mutations). Tumor heterogeneity and antigen loss variants pose significant challenges to consistent immune targeting. The TME comprises tumor cells, immune cells, fibroblasts, endothelial cells and the extracellular matrix (ECM), all of which influence immune responses [3].

Induces HIF-1α, which promotes VEGF-mediated angiogenesis and immune evasion. Tumor cells consume glucose and produce lactate, impairing T cell metabolism and function. Tumor-derived exosomes carry immunosuppressive molecules that reprogram immune cells. Dense ECM impedes immune cell infiltration and supports mechanical resistance to therapy. Chronic inflammation, often driven by infection or irritants, contributes to oncogenesis. Immune cells in such environments produce reactive species and cytokines. Facilitate Epithelial-Mesenchymal Transition (EMT). Cancers like hepatocellular carcinoma, gastric cancer and colorectal cancer are closely linked to chronic inflammatory states. Under continuous immune pressure, tumors undergo immunoediting. This evolutionary arms race underlines the need for multi-targeted and adaptive immunotherapies [4].

Anti-PD-1, anti-PD-L1 and anti-CTLA-4 antibodies have transformed care in melanoma, lung and renal cancers. Limited response rates, immune-related adverse events (irAEs), resistance. CAR-T cells and TIL therapies bypass native recognition mechanisms. Limitations in solid tumors due to TME barriers and antigen heterogeneity. Personalized neoantigen vaccines offer a tailored approach. Limited efficacy without strong adjuvants or immune priming. Selectively infect and lyse tumor cells while stimulating immunity. ICB + radiation/chemotherapy/targeted therapy to enhance immunogenicity. Rational design based on tumor immune profiling is essential. Tumor Mutational Burden (TMB): High TMB predicts neoantigen presence. MSI-high tumors respond well to ICB. Quantitative and spatial analyses guide prognosis. Advanced techniques like single-cell RNA sequencing and spatial transcriptomics are enhancing our ability to profile immune landscapes. As our understanding deepens, novel strategies are being pursued: Bridge immune cells and tumors, enhancing recognition and killing. Target intracellular antigens presented by MHC. Stimulate innate immunity (e.g., STING, TLR agonists). Gut flora influence systemic immunity and therapy outcomes. Predict response and design optimal immunotherapy regimens [5].

Conclusion

The tumor-immune relationship is a dynamic interplay that encompasses protection, evasion and adaptation. While the immune system has the potential to eliminate cancer, tumors exploit immune mechanisms to foster their survival. Understanding this complexity is pivotal to advancing immunotherapy and developing durable, effective treatments. With the integration of immunochemistry, genomics, computational biology and systems immunology, the future holds promise for unlocking the full therapeutic potential of the immune system in combating cancer. Tailored strategies that adapt to the evolving tumor-immune interface will be essential in achieving lasting clinical success and transforming cancer into a manageable or even curable disease.

Acknowledgement

None.

Conflict of Interest

None.

References

1. Sideri, Silvia, Francesco Petragnano, Roberto Maggio and Simonetta Petrungaro, et al. "Radioresistance mechanisms in prostate cancer cell lines surviving ultra-hypo-fractionated EBRT: Implications and possible clinical applications." Cancers14 (2022): 5504.

Google Scholar        Cross Ref                Indexed at

2. Larson, Sandy R., Xiaotun Zhang, Ruth Dumpit and Ilsa Coleman, et al. "Characterization of osteoblastic and osteolytic proteins in prostate cancer bone metastases." Prostate73 (2013): 932-940.

Google Scholar        Cross Ref                Indexed at

3. Calvi, Laura M. "Osteoblastic activation in the hematopoietic stem cell niche."  Ann N Y Acad Sci 1068 (2006): 477-488.

Google Scholar        Cross Ref                Indexed at

4. Shiozawa, Yusuke, Kenneth J. Pienta and Russell S. Taichman. "Hematopoietic stem cell niche is a potential therapeutic target for bone metastatic tumors." Clin Cancer Res 17 (2011): 5553-5558.

Google Scholar        Cross Ref                Indexed at

5. Hofbauer, Lorenz C. and Armin E. Heufelder. "Role of receptor activator of nuclear factor-κB ligand and osteoprotegerin in bone cell biology." J Mol Med 79 (2001): 243-253.

Google Scholar        Cross Ref                Indexed at