Unraveling Immune Dynamics and Novel Therapeutic Strategies in the Tumor Microenvironment

Dear Colleagues,

The tumor microenvironment (TME) represents a highly complex and dynamic ecosystem that plays a pivotal role in cancer initiation, progression, immune evasion, and therapeutic resistance. Within this intricate milieu, tumor cells coexist with immune cells, stromal components, vascular networks, and extracellular matrix structures, creating an environment that profoundly influences disease trajectory and treatment outcomes. The functional interactions between T cells, B cells, macrophages, dendritic cells, and natural killer (NK) cells with tumor cells determine whether the immune response will favor tumor suppression or tumor progression. Despite major advances in immunotherapy, including immune checkpoint inhibitors, adoptive cell therapies such as CAR T cells and tumor-infiltrating lymphocytes (TILs), as well as monoclonal antibodies and combination immunotherapies, the clinical benefits remain limited to a subset of patients. Challenges such as tumor heterogeneity, immune suppression, therapy resistance, and adverse toxicities continue to impede durable responses. Overcoming these barriers requires rigorous experimental investigation to elucidate the cellular and molecular mechanisms that govern immune regulation within the TME. Computational, AI/ML-driven, and physics-based modeling approaches may also aid in identifying therapeutic targets, optimizing protein structures, and engineering next-generation immune cells with enhanced functionality and persistence within the tumor microenvironment.

This Special Issue aims to bring together recent advances in experimental immunology, computational biology, systems immunology, and artificial intelligence to advance our understanding of the TME and promote the development of personalized, durable immunotherapies. Contributions are encouraged from researchers applying single-cell and spatial transcriptomics, computational protein design, deep learning-based modeling, and multi-omics data integration to explore immune–tumor interactions and therapeutic innovation. By emphasizing cross-disciplinary approaches, this issue seeks to highlight transformative strategies that connect molecular insights to clinical translation, fostering collaboration between immunologists, computational scientists, and oncologists. Collectively, the research featured in this issue will enhance our mechanistic understanding of tumor–immune interactions and accelerate the design of next-generation therapies with improved efficacy, selectivity, and persistence.

In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the following (Sample Topics for Submission):

1. Identification of cancer-specific molecular signatures for the rational development of immunotherapies;
2. Targeting the cancer-specific molecular signatures with antibodies, nanobodies, peptides, or aptamers;
3. Single-cell and spatial transcriptomic analyses revealing tumor and immune heterogeneity and cell–cell communication in the TME;
4. Computational and AI-driven protein, antibody, nanobody, and peptide design for precision cancer immunotherapy and checkpoint modulation;
5. Advances in adoptive cell therapies, including CAR T, TIL, and bispecific T cell engager engineering, to improve persistence and overcome immune suppression;
6. Integration of deep learning and systems biology approaches for predicting immune–tumor interactions and therapeutic responses.

Dr. Shahidul M. Islam
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

• tumor microenvironment
• immune dynamics
• tumor heterogeneity
• immune checkpoints
• CAR T
• cancer immunology
• adoptive cell transfer
• resistance
• biomarkers
• combination therapy
• machine learning
• molecular modeling