Methods and compositions for treating an infection or disease that results from (1) failure to elicit rapid T cell mediated responses, (2) induction of T cell exhaustion, T cell anergy or both, or (3) failure to activate monocytes, macrophages, dendritic cells and/or other APCs, for example, as required to kill intracellular pathogens. The method and compositions solve the problem of undesired T cell inhibition by binding to and blocking PD-I to prevent or reduce inhibitory signal transduction, or by binding to Hgands of PD-I such as PD-L1, thereby preventing (in whole or in part) the ligand from binding to PD-I to deliver an inhibitory signal. The immune response can be modulated by providing antagonists which bind with different affinity (i.e., more or less as required), by varying the dosage of agent which is administered, by intermittent dosing over a regime, and combinations thereof, that provides for dissociation of agent from the molecule to which it is bound prior to being administered again (similar to what occurs with antigen elicitation using priming and boosting). In some cases it may be particularly desirable to stimulate the immune system, then remove the stimulation.腫瘍または腫瘍関連新生血管系を標的とし、かつ、腫瘍浸潤Ｔ細胞機能を増強する組成物が提供される。これらの組成物としては、Ｔ細胞結合ドメイン、および腫瘍／腫瘍関連新生血管系標的化ドメインを含む融合タンパク質が含まれる。融合タンパク質は場合により、ペプチド／ポリペプチドリンカードメインおよび二量体化および多量体化を媒介するドメインを含んでもよい。このＴ細胞結合ドメインは共刺激分子である。融合タンパク質を用いて免疫応答を増強する方法が提供される。開示されている組成物の治療的使用は、腫瘍免疫の誘導を含む。
