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Tumor Immunotherapy

Tumor Immunotherapy

Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.

Cytotoxic T Cells-mediated Immune Response

Cytotoxic T Cells-mediated Immune Response

Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...

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Human Immunodeficiency Virus Impairs Immune Responses to Tumor Neoepitopes Without Altering Mutational Profiles in

Baptiste Abbar¹, Karim Labreche², Jacques Cadranel³

¹Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Institut national de la santé et de la recherche médicale (INSERM) U1135, CNRS ERL8255, Sorbonne Université, Paris, France; Department of Medical Oncology, Assistance Publique - Hôpitaux de Paris (AP-HP), Pitié-Salpêtrière Hospital, Institut Universitaire de Cancérologie, Sorbonne Université, Paris, France.

Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer

|February 9, 2025

Summary

This summary is machine-generated.

HIV infection impairs antitumor immunity in non-small cell lung cancer (NSCLC) patients. Despite similar tumor profiles, people living with HIV (PLWHIV) show reduced T-cell responses, especially to MHC class I neoepitopes, impacting immunotherapy effectiveness.

Keywords:

HIV Molecular profile NSCLC Tumor microenvironment Tumor neoepitopes

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Area of Science:

Immunology
Oncology
Virology

Background:

Non-small cell lung cancer (NSCLC) presents a significant challenge for people living with human immunodeficiency virus (PLWHIV), often leading to poor prognosis.
The underlying immunological factors contributing to this disparity remain largely unknown.

Purpose of the Study:

To compare the immunogenomic characteristics and antitumor immune responses between NSCLC patients with and without HIV infection.
To investigate the impact of HIV on neoantigen recognition and T-cell function in the tumor microenvironment.

Main Methods:

Prospective comparison of 27 NSCLC samples (15 PLWHIV, 12 immunocompetent controls).
Comprehensive analysis using whole-exome and RNA sequencing, bioinformatics, ex vivo Interferon gamma (IFNγ) ImmunoSpot assays, and intracellular cytokine staining.
Evaluation of tumor mutational burden, molecular signatures, tumor microenvironment, and neoepitope prediction.

Main Results:

Tumor mutational burden, molecular profiles, and predicted neoepitopes were similar between PLWHIV and immunocompetent patients (ICs).
T-cell responses in PLWHIV were exclusively against MHC class II-restricted neoepitopes, unlike the balanced response in ICs.
PLWHIV exhibited impaired T-cell function, lower neutrophil proportions, and a correlation between low CD4 counts and lack of neoepitope-specific responses.

Conclusions:

HIV infection significantly impairs local and systemic antitumor immune responses in NSCLC patients, particularly against MHC class I-restricted neoepitopes.
These findings highlight the critical need for tailored immunotherapies, such as those targeting MHC class I-restricted neoepitopes, for PLWHIV with NSCLC.