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. 2022 Jun 24;11(1):2093518. doi: 10.1080/2162402X.2022.2093518

Table 1.

Preclinical studies combining ICD inducers and PD-1/PD-L1 blockade.

ICD inducer PD-1 /
PD-L1
Cancer models Treatment procedure Observations Ref
Oxaliplatin + cyclophosphamide PD-1 + CTLA-4 KRAS and TRP53 (KP) mutant lung cancer Sequential Restores the sensitivity of a multi treatment-resistant lung cancer model to PD-1 and CTLA-4 blockade 29
Oxaliplatin + cyclophosphamide PD-L1 KRAS and TRP53 (KP) mutant lung cancer Sequential Enhances recruitment of CAR-T cells to lung tumors and sensitizes tumors to PD-L1 blockade 30
Oxaliplatin or mitoxantrone PD-1 + CTLA-4 Fibrosarcoma Sequential Oxaliplatin combination with CRMs synergize with ICIs 31
Oxaliplatin PD-L1 LLC Simultaneous Oxaliplatin treatment led to increased PD-L1 expression on LLC cells and synergize anti-PD-L1 32
Oxaliplatin PD-1 LLC Simultaneous Oxaliplatin treatment improves tumor infiltration of T and NK cells and synergize αPD-1 24
Oxaliplatin PD-1 Hepatocellular
carcinoma
Sequential Combination therapy of oxaliplatin and αPD-1 exert better anticancer effect than monotherapy 30
Oxaliplatin PD-L1 Colorectal cancer Simultaneous Oxaliplatin boosts anti-PD-L1 effect in an orthotopic colorectal tumor model 33
Oxaliplatin PD-1 + CTLA-4 Colorectal cancer Sequential Oxaliplatin-induced ICD rendered an ICI-resistant preclinical colorectal cancer model to response 34
Oxaliplatin + pemetrexed PD-1 Colorectal cancer Simultaneous Oxaliplatin + pemetrexed increase DC and T cell infiltration, potentiate αPD-1 for regressing murine colorectal cancer. 35
Oxaliplatin + trifluridine/tipiracil PD-1 Colorectal cancer Simultaneous Oxaliplatin + FTD/TPI induce ICD in vivo and potentiate αPD-1 effect 36
Oxaliplatin + capecitabine PD-L1 Colorectal cancer Simultaneous Oxaliplatin + capecitabine potentiate αPD-L1 effects 37
Oxaliplatin + 5-FU PD-1 Gastric cancer Simultaneous Oxaliplatin + 5-FU increase cytotoxic T cell infiltration, deplete MDSCs in gastric tumors and increased the response to αPD-1 38
PT-112 (a platinum-pyrophosphate conjugate) PD-1
PD-L1
Colorectal cancer Sequential PT-112 synergizes with PD-1 or PD-L1 blockade to eradicate established mouse colon tumors 39
Crizotinib in combination with cisplatin PD-1 NSCLC;
fibrosarcoma
Sequential Crizotinib-induced ICD sensitizes αPD-1 in implantable, carcinogen- or oncogene induced orthotopic NSCLC models 40
Ceritinib PD-1 ALCL Sequential Crizotinib and ceritinib induce ICD and synergize with αPD1 in ALK-dependent ALCL 41,42
Dinaciclib PD-1 Colorectal cancer;
bladder cancer
Simultaneous Dinaciclib-induced ICD augments antitumor immunity elicited by αPD-1 43
Lurbinectedin PD-1 + CTLA-4 NSCLC;
fibrosarcoma
Sequential FDA-approved lurbinectedin treatment showed traits of ICD and was boosted in combination with PD-1 and CTLA-4 ICI 44,45
Vinorelbine, cyclophosphamide and 5-FU PD-1
PD-L1
Breast cancer; lymphoma Simultaneous Combination treatment with these chemotherapies synergized with αPD-L1 46
LTX-401 PD-1 + CTLA-4 NSCLC;
fibrosarcoma
Sequential LTX-401 treatment sequentially combined with double ICI exhibited strong abscopal antineoplastic effects 47
Local anesthetics in combination with cisplatin PD-1 Fibrosarcoma; breast cancer; colorectal cancer Sequential Local anesthetics induce ICD and exert synergistic anticancer effect with cisplatin and αPD1 48
Cold atmospheric plasma PD-L1 Melanoma Simultaneous Cold atmospheric plasma elicits ICD in melanoma and augments the antitumor effect of αPD-L1 49,50
Radiotherapy PD-1 NSCLC Sequential Radiotherapy potentiates the effect of αPD-1 in KRAS-driven mouse NSCLC 51
Oncolytic virotherapy PD-1 and CTLA-4 Breast cancer Sequential Oncolytic adenoviruses synergistically enhance anti-PD-L1 and anti-CTLA-4 immunotherapy 52
  PD-1 Fibrosarcoma Sequential Transcription inhibitors exert immunogenic cell killing and sensitize solid tumors to PD-1 blockade 53

5-fluorouracil, 5-FU; anaplastic large cell lymphoma, ALCL; caloric restriction mimics, CRM; chimeric antigen receptor-T cell, CAR-T; immune checkpoint inhibitor, ICI; immunogenic cell death, ICD; Lewis lung carcinoma, LLC; non-small cell lung cancer, NSCLC