Heterogeneity of the tumor immune microenvironment and clinical interventions

doi:10.1007/s11684-023-1015-9

Frontiers of Medicine

2023, Vol. 17

Issue (4): 617-648 https://doi.org/10.1007/s11684-023-1015-9

本期目录

Heterogeneity of the tumor immune microenvironment and clinical interventions

Zheng Jin^1,^2,^3,⁴, Qin Zhou^1,^2,⁵, Jia-Nan Cheng^1,²(

), Qingzhu Jia^1,²(

), Bo Zhu^1,²(

)

¹. Department of Oncology, Xinqiao Hospital, Army Medical University, Chongqing 400037, China
². Key Laboratory of Tumor Immunotherapy, Chongqing 400037, China
³. Research Institute, GloriousMed Clinical Laboratory (Shanghai) Co. Ltd., Shanghai 201318, China
⁴. Institute of Life Sciences, Chongqing Medical University, Chongqing 400016, China
⁵. School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 400054, China

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Abstract：

The tumor immune microenvironment (TIME) is broadly composed of various immune cells, and its heterogeneity is characterized by both immune cells and stromal cells. During the course of tumor formation and progression and anti-tumor treatment, the composition of the TIME becomes heterogeneous. Such immunological heterogeneity is not only present between populations but also exists on temporal and spatial scales. Owing to the existence of TIME, clinical outcomes can differ when a similar treatment strategy is provided to patients. Therefore, a comprehensive assessment of TIME heterogeneity is essential for developing precise and effective therapies. Facilitated by advanced technologies, it is possible to understand the complexity and diversity of the TIME and its influence on therapy responses. In this review, we discuss the potential reasons for TIME heterogeneity and the current approaches used to explore it. We also summarize clinical intervention strategies based on associated mechanisms or targets to control immunological heterogeneity.

Key words： tumor immune heterogeneity clinical intervention tumor microenvironment

收稿日期: 2023-02-15 出版日期: 2023-10-12

Corresponding Author(s): Jia-Nan Cheng,Qingzhu Jia,Bo Zhu

引用本文:

. [J]. Frontiers of Medicine, 2023, 17(4): 617-648.
Zheng Jin, Qin Zhou, Jia-Nan Cheng, Qingzhu Jia, Bo Zhu. Heterogeneity of the tumor immune microenvironment and clinical interventions. Front. Med., 2023, 17(4): 617-648.

链接本文:

https://academic.hep.com.cn/fmd/CN/10.1007/s11684-023-1015-9
https://academic.hep.com.cn/fmd/CN/Y2023/V17/I4/617

Fig.1

Tab.1

Fig.2

Tab.2

Fig.3

Strategies	Therapy	Agent	Cancer type	Trial number	Trial phase
Modulating genetic processes of tumor cells	PARP inhibitors	Olaparib	HER2-negative BC	NCT05340413	Phase II
		Olaparib + pembrolizumab	Metastatic CRC	NCT05201612	Phase II
		Niraparib + pembrolizumab	NSCLC	NCT04475939	Phase III
	TKIs	BPI-7711	NSCLC	NCT03866499	Phase III
		Osimertinib	NSCLC	NCT05120349	Phase III
		EGF816 + gefitinib	NSCLC	NCT03292133	Phase II
		WX-0593 + chemoradiotherapy	NSCLC	NCT05351320	Phase II
Promoting activation of antigen presenting cells	STING agonists	E7766	Solid tumors	NCT04144140	Phase I
		MK1454 + pembrolizumab	HNSCC	NCT04220866	Phase II
		MK1454 + pembrolizumab	Solid tumors, lymphomas	NCT03010176	Phase I
		MIW815	Solid tumors, lymphomas	NCT03172936	Phase I
		SNX281 + pembrolizumab	Solid tumor	NCT04609579	Phase I
	TLR agonists	SD-101 + ICBs	Primary liver tumors	NCT05220722	Phase I/II
		SD-101 + pembrolizumab	Prostatic neoplasms	NCT03007732	Phase II
		VTX-2337 + MEDI4736	Ovarian cancer	NCT02431559	Phase I/II
		SD-101 + pebrolizumab	Pancreatic adenocarcinoma	NCT05607953	Phase I
	CD40 agonists	SEA-CD40 + other drugs	Melanoma, NSCLC	NCT04993677	Phase II
		Selicrelumab	Solid tumors	NCT02304393	Phase I
		APX005M	Ovarian cancer	NCT05201001	Phase II
		APX005M + nivolumab + ipilimumab	Melanoma, RCC	NCT04495257	Phase I
		ADC-1013	Ametastatic pancreatic cancer	NCT05650918	Phase I
T cell priming	Oncolytic viruses	T-VEC	Melanoma	NCT04330430	Phase II
		T-VEC	Melanoma	NCT04427306	Phase II
		H101 + camrelizumab	Bladder cancer	NCT05564897	Phase II
		Gebasaxturev + pembrolizumab	Melanoma	NCT04303169	Phase I/II
		Gebasaxturev + pembrolizumab	Melanoma	NCT04152863	Phase II
	Tumor vaccines	ISA101b	SCC of oropharynx	NCT04398524	Phase II
		ISA101b + pembrolizumab + cisplatin	HPV-related HNSCC	NCT04369937	Phase II
		MAGE-A3	NSCLC	NCT04908111	Phase I/II
		MAGE-A3 + pembrolizumab	Metastatic melanoma	NCT03773744	Phase I
		Galinpepimut	AML	NCT04229979	Phase III
		pTVG-HP + nivolumab	Prostate cancer	NCT03600350	Phase II
		RO7198457 + atezolizumab	NSCLC	NCT04267237	Phase II
		Peptides + poly-ICLC	Melanoma	NCT01970358	Phase I
		RO7198457 + pembrolizumab	Melanoma	NCT03815058	Phase II
		NEO-PV-01 + nivolumab	Melanoma, lung cancer; bladder cancer	NCT02897765	Phase I
Trafficking of T cells into tumors	Antiangiogenic monoclonal antibodies	Bevacizumab + atezolizumab	HCC	NCT04732286	Phase III
		Bevacizumab + osimertinib	Lung cancer	NCT04988607	Phase II
		Bevacizumab + paclitaxel + carboplatin	NSCLC	NCT05654454	Phase III
		Ramucirumab + pembrolizumab	Gastric cancer	NCT04632459	Phase II
		Ramucirumab + atezolimuab + N-803	NSCLC	NCT05007769	Phase II
	Antiangiogenic TKIs	Sorafenib + vemurafenib	Pancreas cancer	NCT05068752	Phase II
		Sorafenib	HCC	NCT05117957	Phase II
		Regorafenib	HCC	NCT04718909	Phase II
		Regorafenib + fulvestrant	Ovarian cancer	NCT05113368	Phase II
		Fruquintinib	CRC	NCT02314819	Phase III
		Anlotinib	NSCLC	NCT02388919	Phase III
T cell reprogramming	CAR-T cells	CEA CAR-T cells	Solid tumors	NCT05538195	Phase I/II
		CEA CAR-T cells	Solid tumors	NCT05415475	Phase I
		U87 CAR-T cells	Pancreatic cancer	NCT05605197	Phase I
		CD70 CAR-T cells	Advanced/metastatic solid tumors	NCT05518253	Phase I
		B7H3 CAR-T cells	Liver cancer	NCT05323201	Phase I/II
		IM92 CAR-T cells	Gastric or pancreatic cancer	NCT05275062	Phase I
		Anti-PD-L1 armored anti-CD22 CAR-T cells	Solid tumors	NCT04556669	Phase I
		NKG2D CAR-T cells	Metastatic CRC	NCT05248048	Phase I
	TCR-T cells	TCR-T cells	Pancreatic cancer	NCT05438667	Phase I
		E7 TCR-T cells	HPV-related cancers	NCT05686226	Phase II
		MAGE-C2 TCR-T cells	Melanoma, HNSCC	NCT04729543	Phase I/II
		SCG101	HBV-related HCC	NCT05417932	Phase I/II
		AFP TCR-T	HCC	NCT03132792	Phase I
	TILs	TILs + CAR-TILs	Solid tumors	NCT04842812	Phase I
		TILs	Solid tumors	NCT04967833	Phase I
		TILs	Melanoma	NCT05098184	Phase I
		C-TIL051	Metastatic NSCLC	NCT05676749	Phase I
		ScTIL	Solid tumors	NCT04571892	Phase I/II
Inhibition of tumor immune evasion	A2aR blockades	Ciforadenant + daratumumab	Multiple myeloma	NCT04280328	Phase I
		AZD4635 + durvalumab + cabazitaxel	Metastatic CRPC	NCT04495179	Phase II
		Inupadenant	Solid tumors	NCT05117177	Phase I
	Anti-CD73 antibodies	Oleclumab + durvalumab	Metastatic sarcoma	NCT04668300	Phase II
		Sym024	Solid tumors	NCT04672434	Phase I
		AK119	Solid tumors	NCT05173792	Phase I
	Anti-CD39 antibodies	TTX-030 + immunotherapy/chemotherapy	Solid tumors	NCT04306900	Phase I
		IPH5201	Solid tumors	NCT04261075	Phase I
		SRF617	Solid tumors	NCT04336098	Phase I
	TGF-β inhibitors	M7824	HNSCC	NCT04247282	Phase I/II
		Vactosertib + pembrolizumab	NSCLC	NCT04515979	Phase II
		Galunisertib + capecitabine	Advanced CRC	NCT05700656	Phase I/II
		SRK-181 + anti-PD-(L)1 antibody	Solid tumors	NCT04291079	Phase I
	IDO1 inhibitors	Epacadostat	Urothelial carcinoma	NCT04586244	Phase II
		Epacadostat	Rectal cancer	NCT03516708	Phase I
		BMS-986205	Solid tumors	NCT03459222	Phase I/II

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