Cell- and immunotherapies have transformed the treatment landscape for many hematological diseases. In some patients, these treatments induce durable responses that were previously difficult to achieve. In others, the same therapeutic approach results in limited or transient effects, even when the underlying diagnosis appears comparable. Given how strongly immune function depends on coordinated interactions between cells, this variability is perhaps not surprising. Immunotherapy response does not arise from the presence of specific cell types alone, but from how therapeutic cells engage with their target cells and with the surrounding cellular microenvironment. Understanding why these interactions succeed in some settings and fail in others remains one of the central challenges in the field.

In practice, much of cell- and immunotherapy research has focused on characterizing the cellular components of the immune system. Significant effort goes into defining cell types, activation states, and molecular profiles, with the expectation that increasingly detailed descriptions will translate into better predictions of therapeutic behavior. This approach has enabled more precise classification of immune populations and has supported the development of increasingly targeted therapies. At the same time, it rests on the assumption that understanding individual cells in sufficient detail will be enough to explain therapeutic function. In practice, immune responses rarely emerge from isolated cells. They are driven by interactions. Cells come into contact, disengage, re-engage, or fail to interact altogether. These encounters are shaped by timing, spatial context, and local conditions, and they often determine whether an immune response is initiated, sustained, or extinguished. This becomes particularly apparent in cell-based therapies. A therapeutic cell, such as a CAR-T or TCR-T cell, can exhibit the expected molecular features and still fail to produce a meaningful effect. In these cases, the limitation is not necessarily the cellular identity or activation state of the cell, but the nature of its interactions with other cells in the microenvironment. 

Cell-cell interactions play a central role in a wide range of physiological processes, including tissue homeostasis, organismal development, and immune function. Despite their well-established importance, there are currently no widely adopted technologies that allow cell-cell interactions to be measured directly and at scale. As a result, researchers and clinicians have had limited opportunity to use cellular interaction patterns themselves as a primary readout. Instead, cell communication is most often inferred indirectly through downstream signals or summarized in bulk measurements (e.g. in sequencing technologies). This reflects longstanding technical challenges in capturing interactions in a systematic and scalable manner, as well as the fact that existing experimental workflows have been built around more accessible measurements. The consequence is that a central aspect of immune function remains underrepresented in how therapies are evaluated and compared. An alternative way of thinking about immunotherapy is to view it less as a collection of engineered or activated cells and more as a dynamic system defined by patterns of interaction. From this perspective, function is not solely encoded in static cellular properties, but in how cells engage with one another over time. Taking this view seriously would shift what is considered informative in early research and drug development. Assays would be judged not only by how well they describe cells, but by how well they capture functional engagement, interaction and communication. Decisions about drug candidate selection or optimization might rely more on interaction behavior and less on proxy markers alone.

None of this diminishes the importance of single-cell profiling. It remains foundational. The question is whether single-cell analysis alone is sufficient to explain why therapies succeed in some settings and fail in others. Cell-cell interactions have long been recognized as biologically important. What has been less clear is how to integrate them consistently into the practical realities of immunotherapy development. As methods for observing these interactions continue to mature, that gap becomes harder to ignore. Whether and how this perspective will change standard practice remains to be seen. What seems increasingly evident is that understanding immunotherapy response may require paying closer attention not only to the cells involved, but to the interactions that give rise to their function.