About this Research Topic
Excess immunosuppression and insufficient immune effector cell responses underlie the tumor immune evasion that promotes tumor growth. During tumor progression, immune cells that belong to both the adaptive and innate arms of the immune system often exhibit phenotypic and functional instability and transdifferentiate into different cell types or states, promoting or inhibiting the tumor growth or metastasis. For example, regulatory T cells (Treg) become unstable upon the loss of FoxP3 or Nrp-1 in the face of growing tumors. Switching from one T helper (TH) cell subset to another TH subset often takes place in response to environmental cues, such as cytokine signals. NK cells in the tumor can lose anti-tumor capacity and convert into pro-tumoral type 1 innate lymphoid cells (ILC1). Additionally, the M1 type of macrophages or microglia often develop an M2 phenotype to promote tumor progression. Of interest, immune cells within the tumor microenvironment often acquire features of tumor residency, which can further complicate the overall immune responses against tumors.
The molecular mechanisms underlying this immune cell reprogramming may vary depending on the different immune cell types and the environment where they are present. On the one hand, the genetic, epigenetic, and metabolic changes derived from tumors can influence the lineage determination of immune cells in the tumor. On the other hand, the intrinsic regulation of a particular immune cell type at the genetic, epigenetic, and metabolic levels may also contribute to its reprogramming. Since the immune cell lineage reprogramming is likely reversible, it is potentially targetable for new therapeutic interventions. For example, approaches that promote the conversion of Treg into effector T cells may boost anti-tumor effects and inhibit tumor growth.
This Research Topic welcomes Original Research and Review articles to discuss the mechanisms of immune cell reprogramming in the context of cancer, as well as the therapeutic potential of targeting the plasticity of immune cells for the treatment of cancer. Submissions may focus on, but are not limited to, the following subtopics:
1. Extrinsic factors or signals from the tumor microenvironment that dictate the plasticity or stability of immune cells
2. Intrinsic molecular mechanisms that regulate reprogramming of immune cells within the tumor at the genetic, epigenetic (including microRNA, long non-coding RNA) and metabolic levels
3. Impact of the lineage reprogramming of one immune cell type on the other immune cells and tumor growth or metastasis
4. The immune cell lineage reprogramming as predictive or prognostic biomarkers for cancer outcomes or response to the treatment of cancer
5. Novel therapeutic approaches that regulate or target immune cell lineage reprogramming in the treatment of cancer
Topic Editor Dr. Lewis Shi received financial support from Varian Medical System, Inc. The other Topic Editors declare no competing interests with regard to the Research Topic subject.
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.