The tumor microenvironment is composed of a variety of different cell types that work in concert to support or limit the growing tumor. One major component of the tumor microenvironment is the immune system which has spawned a new and hopeful generation of cancer treatment.

Cell-cell communication is key to activating immune responses. Under normal physiological conditions, innate immune responses are necessary to activate T cells through antigen presentation, co-stimulation, and the production of inflammatory cytokines. This heterotypic relationship is critical for the development of adaptive immunity and for the maintenance of tissue homeostasis. However, in the context of cancer, these relationships within the TME can be hijacked by factors expressed by tumor cells or by alternative cell types in the microenvironment, such as blood or lymphatic endothelial cells, adipocytes and fibroblasts. Immune cells that become activated in this context frequently blunt anti-tumor adaptive immune responses, thus leading to immune evasion by the tumor and tolerance. Understanding the network of communication between multiple cell types within the microenvironment is key to understanding how to block immune evasion and to stimulate anti-tumor immune responses.

This Research Topic will focus on heterotypic communication within the TME during cancer progression and response to therapy, with a core focus on the intersection between innate and adaptive immunity in the TME. While there are a myriad of studies focused on the influence of individual immune cell types in cancer, there is a growing need to consolidate these findings to gain a broader understanding of the dynamics of the immune network as a whole in cancer. This is particularly important in light of a growing interest in checkpoint inhibitors, which aim to boost adaptive immune responses.

In this Research Topic, we welcome the submission of Reviews, Mini-Reviews, and Original Research articles that can offer thought-provoking, innovative ideas and new insights into the following sub-topics related to the TME:

1. Microenvironmental regulation of innate and adaptive immunity and the interplay between both arms of the immune system.
2. Myeloid-lymphoid communication in cancer.
3. Myeloid-endothelial communication during vascular inflammation and metastasis.
4. Macrophage-T cell dynamics in cancer.
5. Cross-talk between TME cells during malignancy.
6. Predicting and optimizing cellular responses to therapeutic strategies that target the TME.
7. Novel therapies and combinations that reprogram the dysfunctional TME by interfering with cellular cross-talk.

Keywords: TIME, Innate immunity, Adaptive immunity, Cancer immunotherapy, Inflammation, Microenvironment, Metabolism

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.