Harnessing Immunopathology to Understand the Complexities of Cancer Immunity

Preugszat Rosser^*
*Correspondence: Preugszat Rosser, Department of Clinical Immunology, Poznan University of Medical Sciences, 61-701 Pozna, Poland, Email:

Introduction

The relationship between the immune system and cancer is intricate, dynamic and paradoxical. While the immune system has evolved to detect and eliminate abnormal cells, tumors often develop mechanisms to evade immune surveillance and manipulate immune responses to support their own growth. Immunopathology-the study of immune system dysfunction in disease-has emerged as a powerful lens through which to understand the nuances of cancer immunity. By examining the immunological processes that underlie tumor progression, immune evasion and treatment resistance, immunopathology provides critical insights that inform diagnostics, prognostics and therapeutic strategies [1].

Cancer immunology has undergone a renaissance, with breakthroughs in immune checkpoint inhibitors, adoptive T-cell therapies and cancer vaccines reshaping the landscape of oncology. However, therapeutic outcomes vary widely among patients and cancer types, reflecting the complex immunopathological interactions within the Tumor Microenvironment (TME). This explores how immunopathological approaches enhance our understanding of cancer immunity, illuminate key cellular and molecular players and drive the development of next-generation immunotherapies [2].

Description

The immune system's role in cancer encompasses both tumor suppression and promotion. This duality is captured in the concept of cancer immunoediting, which describes three sequential phases. Immune cells recognize and destroy nascent tumor cells. Natural killer (NK) cells, Cytotoxic T Lymphocytes (CTLs), macrophages and dendritic cells. A balance between tumor cell proliferation and immune-mediated killing. Immune pressure selects for resistant tumor variants. Tumor cells evade immune detection and grow unchecked. Mechanisms include downregulation of antigen presentation, upregulation of immune checkpoints and creation of an immunosuppressive TME. Understanding these phases through an immunopathological lens provides a framework for studying how tumors interact with the immune system over time. PD-L1 expression on tumor cells binds PD-1 on T cells, leading to T cell exhaustion. Tumors may downregulate MHC class I or mutate neoantigens to avoid recognition. Chronic inflammation supports tumor initiation, progression and metastasis. Inflammatory cells produce reactive oxygen species, cytokines and matrix-degrading enzymes. M2-polarized TAMs enhance tumor growth, suppress immunity and facilitate metastasis [3].

Defective dendritic cell function impairs the priming of tumor-specific T cells. Loss of co-stimulatory signals further reduces T cell activation. Identify immune infiltrates and checkpoint molecule expression in tumor biopsies. Assess spatial distribution of immune cells. Techniques such as multiplex IHC and imaging mass cytometry provide high-resolution spatial data. Phenotypic and functional profiling of immune cells from tumor and blood samples. Uncovers immune cell heterogeneity and activation states at single-cell resolution. Maps gene expression within tissue architecture to understand immune-tumor interactions. Tracks clonal expansion and diversity of adaptive immune responses. High mutational burden and neoantigen load make it highly immunogenic. Smoking-related mutations increase immunogenicity. Tumor PD-L1 expression guides immunotherapy decisions. Microsatellite instability-high (MSI-H) tumors exhibit strong immune infiltrates and respond to PD-1 blockade. Triple-negative subtype shows higher immune infiltration. Limited checkpoint therapy success; ongoing trials explore combination strategies [4].

B-cell lymphomas and leukemias show variable immune landscapes. CAR-T cell therapies and monoclonal antibodies have shown efficacy. Evaluated via IHC; used to guide use of anti-PD-1/PD-L1 therapies. High TMB correlates with neoantigen load and immunotherapy responsiveness. Predictive of immunotherapy efficacy in CRC and other tumors. Presence and density of tumor-infiltrating lymphocytes inform prognosis. Immune-related gene panels stratify tumors into hot (inflamed) vs. cold (non-inflamed). Anti-CTLA-4, anti-PD-1 and anti-PD-L1 therapies release brakes on T cells. Resistance mechanisms include T cell exclusion, exhaustion and alternative checkpoints. CAR-T cells engineered to recognize tumor antigens. Tumor-infiltrating lymphocyte (TIL) therapy harnesses patientâ??s own T cells. Personalized neoantigen vaccines aim to prime immune responses. Engineered to infect and lyse tumor cells, releasing antigens and boosting immunity. ICB with radiation, chemotherapy, or targeted agents to enhance immunogenicity. Immunopathological studies revealed roles of β-catenin signaling in T cell exclusion. Organized immune aggregates within tumors correlate with improved outcomes. Serve as local sites of antigen presentation and T/B cell priming. Immunopathological analysis of affected tissues (e.g., colitis, pneumonitis) guides management. Inter-patient and intra-tumoral variability complicates treatment design. Immune composition evolves with tumor progression and therapy. Longitudinal sampling and real-time monitoring are needed. Combining genomic, transcriptomic, proteomic and spatial data. Tailoring treatment based on immunopathological profiling [5].

Conclusion

Immunopathology offers a powerful framework to unravel the complexities of cancer immunity. By dissecting the cellular and molecular interactions within the tumor microenvironment, it provides critical insights into mechanisms of immune evasion, resistance and therapeutic response. As the field advances, integrating immunopathological insights with emerging technologies promises to refine our understanding of tumor-immune dynamics and drive the development of more effective, personalized immunotherapies. In the era of precision oncology, harnessing immunopathology is not just an academic endeavor but a clinical imperative that holds the key to transforming cancer care.

Acknowledgement

None.

Conflict of Interest

None.

References

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