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Table 2 Overview of checkpoint inhibitor regimen, bacterial and non-bacterial challenges, and antibiotic regimen in each experiment analyzed from the retrieved studies

From: Checkpoint inhibitor therapy in preclinical sepsis models: a systematic review and meta-analysis

Study (author, year)

Exp ID

Checkpoint inhibitor regimen*

Bacterial challenge**

Additional non-bacterial challenge

Challenge regimen

Antibiotic regimen

Challenge regimen

Antimicrobial regimen

Target

Time@

Dose

Route

Type

Site

Dose

Type

Time@

Type

Time@

Site

Dose

Type

Time@

Route

Seo, 2008

1

PD-L1

D-1

200 μg

IP

L. mono

IV

30000 CFU

NR

NR

NA

Zhang, 2010

1

PD-L1

D-1

50 μg

IP

CLP

IP

NA

NR

NR

NA

2

PD-L1

D0&

50 μg

IP

CLP

IP

NA

NR

NR

NA

Kobayashi, 2013

1

BTLA#

D0^^

400 μg

IP

LPS

IP

750 μg

NA

NA

NA

Cheng, 2016

1

BTLA#

D-1

25 μg/g

IV

CLP

IP

NA

NR

NR

Hem

D-1

NA

D0

25 μg/g

IP

Deng, 2018

1

PD-L1

D0,+1,+2,+3@@

20 mg/kg

NR

CLP

IP

NA

NR

NR

NA

2

PD-L1

D0,+1,+2,+3@@

20 mg/kg

NR

CLP

IP

NA

NR

NR

NA

Patil, 2018

1

PD-L1

D-1

50 μg

IP

P. aer

ID

1x106 CFU

NR

NR

Burn

D-4

Skin

NA

2

PD-L1

D-1

200 μg

IP

S. aur

IV

1x108 CFU

NR

NR

Burn

D-4

Skin

NA

Brahmamdam, 2010

1

PD-1

D+1, +2

200 μg

IV

CLP

IP

NA

NR

NR

NA

Inoue, 2011

1

CTLA-4

D0,+1@@, &&

50 μg

IP

CLP

IP

NA

Imi

D0

NA

2

CTLA-4

D0, +1

200 μg

IP

CLP

IP

NA

Imi

D0

NA

3

CTLA-4

D0,+1, +2@@

50 μg

IP

CLP

IP

NA

Imi

D0

NA

4

CTLA-4

D+6,+9,+11

33 μg

IP

CLP

IP

NA

Imi

D0

C. alb

D+4

IV

UC

NR

NR

NR

Chang, 2013

1

PD-1

D+5,+8,+11

200 μg

IP

CLP

IP

NA

Imi

D+1

C. alb

D+3

IV

UC

Fluc

D+9-12

IP

2

PD-L1

D+5,+8,+11

200 μg

IP

CLP

IP

NA

Imi

D+1

C. alb

D+3

IV

UC

Fluc

D+9-12

IP

3

CTLA-4

D+4

100 μg

IP

CLP

IP

NA

Imi

D+1

C. alb

D+3

IV

UC

Fluc

D+9-12

IP

Shindo, 2015

1

PD-1

D+4,+8

200 μg

IP

CLP

IP

NA

Imi

D0

C. alb

D+3

IV

UC

Fluc

D+5,+6

IP

Shindo, 2017

1

PD-L1^

D+5 to D+13 (TID)

3 mg/kg

SC

CLP

IP

NA

Imi

D0

C. alb

D+3

IV

UC

NR

NR

NR

  1. Exp ID experiment identification number within a study, PD-1 programmed cell death 1, PD-L1 programmed cell death ligand-1, CTLA-4 cytotoxic T lymphocyte-associated protein-4, BTLA B and T lymphocyte attenuator, ID intradermal, IP intraperitoneal, D day, L. mono L. monocytogenes, P. aer Pseudomonas aeruginosa, S. aur Staphylococcus aureus, IV intravenous, SC subcutaneous, CFU colony-forming unit, NR not reported, NA not applicable, CLP cecal ligation and puncture, C. alb Candida albicans, Imi imipenem 1 mg total or 2.5 mg/kg administered subcutaneously, UC unclear, Fluc fluconazole 200 μg, TID dose administered 3 times daily, Hem hemorrhage
  2. *All CPIs were monoclonal antibodies except Shindo 2017 (^), which employed a peptide inhibitor
  3. #The antibody targeting BTLA has been suggested to have both agonistic and antagonistic properties
  4. **Bacterial challenge was designated time 0 (D0) in all experiments
  5. @Time for all treatments and additional challenges in reference to the bacterial challenge at D0
  6. @@Experiments 1 and 3 in Inoue 2011 performed in CD1 and C57BL6 mouse strains respectively and experiments 1 and 2 in Deng 2018 performed in C57BL6 and Bmal-/- mice respectively
  7. ^^Animals treated 30 min before, at the time of, or 30 min after LPS challenge were combined for analysis, see the “Methods” section
  8. &CPI treatment was 3 h after CLP
  9. &&CPI treatment was 6 h after CLP