Dear Colleagues,

We proposed the concept of innate biological nano confinements (iBNCs), by which we may rationally elucidate the priorities of solid tumors on utilization of energy and substances at hypoxia, and less nutrition supplying environments both extra- and intra-cellular. The ultimate objective was to address the confusion that CAR-T therapies are effective for hematological cancers but less effective for solid tumors and also to reveal the fact that CAR-T adjuvant therapy with chemotherapy has synergetic enhancement effects.

CAR-T has proved with great strength in blood cancer therapy. However, for solid tumors, CAR-T therapy has achieved limited effect. What’s the reason? A previous study suggests that CAR-T therapy has a drawback: T cells entering solid tumors may stop working because of a ‘T-cell failure’ (T cell exhaustion) phenomenon. Clinical CAR-T treatment is usually carried out with monoclonal antibodies (mAbs) due to the limited efficacy of independent use. Although chemotherapy has significant efficacy in hematological tumors, drug resistance is particularly obvious, often accompanied by severe adverse effects. While after CAR T cell re-transfusion, this resistance was reduced; why? Given the blood and lymphatic have higher fluidity, which was not conducive to the formation and maintenance of iBNCs, thereafter the cancer cells lose priority in the competition of energy and essential substances utilization with normal cells, and concurrent with the specific targeted CAR-T cells attacking, cancer cells become sensitive to the therapeutic interventions, and ultimately showed the good curative effect. On the other hand, CAR-T re-transfusion might have potentially disturbed the cancer cell signaling pathway, thereby regulating the trogocytosis to recruit components from normal cells to construct iBNCs, eventually causing iBNCs collapse. Regarding the solid tumors, a relatively stable environment can facilitate the cancer cells to construct iBNCs, to some extent, making cancer cells resistant to drugs and feasible to proliferate.

In this special issue, all article types are welcome including original research articles, review articles, clinical trials, case reports, commentaries, correspondence articles, short reports, etc.