NK Cells, Tumor Cell Transition, and Tumor Progression in Solid Malignancies: New Hints for NK-Based Immunotherapy?

Area of Science:

• Immunology
• Cancer Biology
• Cellular Oncology

Background:

• Natural killer (NK) cells are crucial for early tumor surveillance but struggle against established solid tumors.
• Factors limiting NK cell efficacy include tumor cell invasiveness, a suppressive tumor microenvironment, and tumor complexity.
• The dynamic interplay between NK cells and transitional tumor cells is not well understood.

Purpose of the Study:

• To explore the poorly understood cross-talk between NK cells and tumor cells during different transitional phases.
• To investigate how NK cells might influence tumor cell evolution and susceptibility to immune responses.
• To examine the role of NK cells at tumor borders, where Epithelial-to-Mesenchymal Transition (EMT) occurs.

Main Methods:

• In vitro studies analyzing NK cell-tumor cell interactions.
• Immunohistochemical analyses of tumor biopsies.
• Investigation of molecular markers like HLA-I, PD-L1, NKG2D-L, and HMGB1.

Main Results:

• NK cells may not only kill tumor cells but also induce changes in their phenotype, including HLA-I, PD-L1, and NKG2D-L expression.
• NK cells are often found at tumor borders where tumor cells undergo Epithelial-to-Mesenchymal Transition (EMT) and acquire a prometastatic phenotype.
• High-mobility group box 1 (HMGB1) is implicated in both EMT and NK cell recruitment, suggesting a role in tumor progression.

Conclusions:

• NK cells possess a dual role, capable of eliminating early tumors and influencing the evolution of established tumors.
• The interaction between NK cells and tumor cells, especially during EMT, can modulate tumor metastatic potential and immune evasion.
• Further research into NK cell-tumor cell dynamics, particularly involving HMGB1, is warranted to understand their impact on cancer progression.