Cytotoxic lymphocytes (CTLs) play a crucial role in antitumor immunity, forming the backbone of the body’s defense against cancer. Traditionally, CD8⁺ T cells and natural killer (NK) cells have been considered the primary cytotoxic effectors; however, recent insights have broadened this field to include γδ T cells, natural killer T (NKT) cells, type 1 innate lymphoid cells (ILC1s), and cytotoxic CD4⁺ T cells. These diverse and dynamic populations contribute to a complex immune modulation network within the tumor microenvironment (TME), orchestrating an intricate defense against tumor development and progression. Despite this recognized importance, gaps remain in understanding key aspects: the modulation these cells undergo within the TME, the factors that influence their cytotoxic potential, and their role in cancer progression or suppression.
The latest advances in research techniques, such as single-cell transcriptomics, epigenomics, and spatial profiling, have unearthed previously hidden subsets of cytotoxic lymphocytes, revealing distinct differentiation pathways and vulnerabilities specific to different states. In addition, multiomics approaches integrating transcriptomic, proteomic, and metabolomic data have started to unravel how metabolic stress, signaling networks, and immune checkpoints work together to define cytotoxic lymphocyte efficacy within the TME. These advancements help in decoding the complex interactional dynamics between cytotoxic lymphocytes and their environment, thus providing a clearer picture of their role in cancer biology.
This Research Topic aims to deepen the understanding of how cytotoxic lymphocytes function within the TME, spotlighting their diversity and plasticity. By focusing on the varied mechanisms that guide these cells' actions, exhaustions, and potential to influence immunotherapeutic strategies, we hope to pave the way for innovative breakthroughs in cancer treatment.
To gather further insights in the boundaries of cytotoxic lymphocyte interactions, we welcome articles addressing, but not limited to, the following themes:
-Elucidating classical cytotoxic pathways (perforin–granzyme, Fas/FasL, TRAIL) alongside emerging regulatory mechanisms. -Exploring the unique contributions of unconventional cytotoxic subsets (γδ T cells, NKT cells, ILC1s, CD4⁺ CTLs) to tumor control. -Investigating the mechanistic pathways shaping cytotoxic cell function, exhaustion, plasticity, and cellular crosstalk in the TME, including studies employing spatial genomics, epigenetics, and single-cell approaches. -Providing translational insights linking cytotoxic lymphocyte biology to immunotherapeutic strategies.
The Topic Editors declare no conflicts of interest
Article types and fees
This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:
Brief Research Report
Case Report
Classification
Clinical Trial
Editorial
FAIR² Data
General Commentary
Hypothesis and Theory
Methods
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Article types
This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:
Brief Research Report
Case Report
Classification
Clinical Trial
Editorial
FAIR² Data
General Commentary
Hypothesis and Theory
Methods
Mini Review
Opinion
Original Research
Perspective
Review
Study Protocol
Systematic Review
Technology and Code
Keywords: tumor microenvironment, Cytotoxic lymphocytes, CD8 T cells, NK cells, γδ T cells, NKT cells, ILC1s, immune checkpoints, single-cell transcriptomics, cancer immunotherapy
Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
