Which type of immune cell is responsible for spontaneous antitumor activity?

Spontaneous Antitumor Activity is a Function of Natural Killer Cells

Spontaneous antitumor activity is primarily a function of natural killer (NK) cells (e), which can recognize and kill tumor cells without prior sensitization or activation. 1, 2

Characteristics of Natural Killer Cells

Natural killer cells are lymphocytes that possess the unique ability to spontaneously recognize and destroy malignantly transformed cells without requiring prior immunization or activation. They represent approximately 10-15% of peripheral blood mononuclear cells and have the following key features:

• Immunophenotype: CD3-, TCR-, surface Ig-, CD56+, CD16+, CD94/NKG2D+, CD158a+, CD158b+, CD161+, FasL+ 3
• Morphology: Large granular lymphocytes with azurophilic granules in their cytoplasm 4
• Mechanism of action: Direct cytotoxicity through release of proteolytic enzymes (perforin, granzymes) and induction of apoptosis 3

Mechanisms of NK Cell Antitumor Activity

NK cells employ two primary mechanisms to destroy malignant cells:

1. Spontaneous cytotoxicity: A major histocompatibility complex (MHC)-independent process where NK cells directly recognize and kill tumor cells 3

   • NK cells preferentially attack cells that lack expression of MHC class I antigens 2
   • This allows NK cells to identify and eliminate "missing self" on malignantly transformed cells

2. Antibody-dependent cellular cytotoxicity (ADCC): NK cells bind to antibody-coated tumor cells via their Fc receptors (CD16) and induce cell lysis 3

Distinction from Other Immune Cells

Unlike other immune cells that may have antitumor activity:

• Cytotoxic T cells (c): Require prior sensitization, exhibit clonally distributed specificity, are restricted by MHC, and demonstrate immunological memory 5
• B lymphocytes (b): Produce antibodies but lack direct spontaneous cytotoxic activity against tumor cells
• Helper T cells (d): Support immune responses but don't directly kill tumor cells; they activate cytotoxic T cells that require prior sensitization 6
• Macrophages (a): Can kill tumor cells but typically require activation and don't exhibit spontaneous cytotoxicity

Role of NK Cells in Cancer Immunosurveillance

NK cells are critical components of the innate immune system's defense against cancer:

• They provide immediate, first-line defense against malignantly transformed cells 2
• NK cells have been shown to play a crucial role in controlling tumor growth and metastasis in animal studies 2
• They recognize tumors through various activating receptors and costimulatory molecules 2
• NK cells release cytokines and chemokines that induce inflammatory responses and influence subsequent adaptive immune responses 7

Clinical Relevance

The understanding of NK cell function has significant implications:

• NK cell activity has been shown to be stage-dependent and often lower in various tumor types 3
• The mechanism by which NK cells discriminate between tumor cells and normal cells has provided new insights into tumor immunosurveillance 2
• NK cell manipulation holds promise for improving antitumor immunotherapy 7
• Impaired NK cell function results in diminished surveillance and elimination of malignant cells 6

In conclusion, while multiple immune cell types contribute to antitumor immunity, natural killer cells are uniquely characterized by their ability to spontaneously recognize and kill tumor cells without prior sensitization, making them the correct answer to this question.