Table 3.

Mechanisms summary on hyper-progression after immunotherapy

Tumor cells	Tumor microenvironment
1. Loss of expression of tumor-associated antigens[43] 2. Impairment of antigen processing and delivery[44] 3. Persistent upregulation of PD-L1 expression on the surface of tumor cells[45] 4. Apoptotic resistance in tumor cells[46,47] 5. Induced dormancy and senescence of tumor cells[48] 6. Tumor cells undergo dedifferentiation and EMT[49] 7. MDM2/MDM4 amplification and EGFR mutation[58]	Treg cells	1. Competition with conventional T cells for IL-2 via Foxp3[66,136] 2. Secretion of the anti-inflammatory cytokines TGFβ, IL-10, and IL-35[68,69] 3. The dual expression of CD39 and CD73; the CTLA-4-mediated downregulation of CD80 and CD86 on the surface of APCs[71,73] 4. Production of FGL2 to suppress CD8+ T cells and APCs through FcγRIIb[74,137] 5. Express PD-1 receptors 6. A spatial ecological niche dedicated to immunosuppression[76]
	T cells	1. Release the cytokines IFNγ[80], IL-17[86,87], IL-22[88,89], TNFα[90,91], and IL-6[92] 2. The combination of multiple cytokines, such as TGFβ and TNFα[80] or IFNγ and TNFα[93] 3. The binding of CD27 receptor to CD70 ligand[94]
	B cells	IgG4 competes with IgG1 to bind to Fc receptors on the surface of immune effector cells[107]
	Fc receptor	The binding of the Fc region of the anti-PD-1 antibody to the macrophage FcγR[62]