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Identification and Characterization of Neoantigens As Well As Respective Immune Responses in Cancer Patients
Eva Bräunlein1, Angela M Krackhardt1,2
1Medizinische Klinik III, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
Abstract:
Cancer immunotherapy has recently emerged as a powerful tool for the treatment of diverse advanced malignancies. In particular, therapeutic application of immune checkpoint modulators, such as anti-CTLA4 or anti-PD-1/PD-L1 antibodies, have shown efficacy in a broad range of malignant diseases. Although pharmacodynamics of these immune modulators are complex, recent studies strongly support the notion that altered peptide ligands presented on tumor cells representing neoantigens may play an essential role in tumor rejection by T cells activated by anti-CTLA4 and anti-PD-1 antibodies. Neoantigens may have diverse sources as viral and mutated proteins. Moreover, posttranslational modifications and altered antigen processing may also contribute to the neoantigenic peptide ligand landscape. Different approaches of target identification are currently applied in combination with subsequent characterization of autologous and non-self T-cell responses against such neoantigens. Additional efforts are required to elucidate key characteristics and interdependences of neoantigens, immunodominance, respective T-cell responses, and the tumor microenvironment in order to define decisive determinants involved in effective T-cell-mediated tumor rejection. This review focuses on our current knowledge of identification and characterization of such neoantigens as well as respective T-cell responses. It closes with challenges to be addressed in future relevant for further improvement of immunotherapeutic strategies in malignant diseases.
Insights
Cancer immunotherapy utilizes immune checkpoint modulators to treat advanced cancers. Neoantigens, altered peptides on tumor cells, are crucial for T-cell-mediated tumor rejection, guiding future immunotherapeutic strategies.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Cancer immunotherapy, particularly immune checkpoint modulators like anti-CTLA4 and anti-PD-1/PD-L1 antibodies, has shown significant efficacy in treating advanced malignancies.
- The precise mechanisms underlying the efficacy of these therapies are complex, but emerging evidence highlights the critical role of neoantigens.
Purpose of the Study:
- To review the current understanding of neoantigen identification and characterization in the context of cancer immunotherapy.
- To explore the relationship between neoantigens, T-cell responses, and the tumor microenvironment in mediating tumor rejection.
- To identify future challenges and directions for improving immunotherapeutic strategies.
Main Methods:
- Review of current literature on cancer immunotherapy, immune checkpoint modulators, and neoantigen research.
- Analysis of studies investigating the sources and characteristics of neoantigens, including mutated proteins and posttranslational modifications.
- Examination of methods for identifying neoantigens and characterizing T-cell responses against them.
Main Results:
- Neoantigens, derived from viral or mutated proteins, are essential peptide ligands presented on tumor cells.
- Altered peptide ligands, arising from posttranslational modifications and altered antigen processing, contribute to the neoantigen landscape.
- T-cell responses against neoantigens are activated by immune checkpoint modulators, playing a key role in tumor rejection.
Conclusions:
- Neoantigens are critical determinants in effective T-cell-mediated tumor rejection during cancer immunotherapy.
- Further research is needed to elucidate the interplay between neoantigens, immunodominance, T-cell responses, and the tumor microenvironment.
- Understanding these factors will be crucial for advancing the development of more effective immunotherapeutic strategies for malignant diseases.
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