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Table 4 Effect of checkpoint inhibitor therapy on blood and tissue bacterial counts and organ injury measures

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

Author, year

Exp ID

Checkpoint molecule target

Challenge

Bacterial counts

Organ injury

Decrease

Increase

No difference

Decrease

Increase

No difference

Models not including antibacterial agents

 Seo, 2008

1

PD-L1

IV L. mono

–

Spleen, liver D+3

–

NR

NR

NR

 Brahmamdam, 2010

1

PD-1

CLP

NR

NR

NR

NR

NR

NR

 Zhang, 2010*

1

PD-L1 (D−1)

CLP

NR

NR

NR

NR

NR

NR

2

PD-L1 (D0)

CLP

Peritoneal, blood D+1

–

–

NR

NR

NR

 Kobayashi, 2013

1

BTLA

LPS

NA

NA

NA

NR

NR

NR

 Cheng, 2016

1

BTLA

CLP

–

–

Peritoneal, blood D+1

–

Lung, kidney D+1

Liver D+1

 Deng, 2018#

1

PD-L1

CLP

Peritoneal, blood D+1, D+2, D+3

–

–

Lung, kidney, liver, muscle, intestine D+1, D+2, D+3

–

–

2

PD-L1

CLP

Peritoneal, blood D+1, D+2, D+3

–

–

Lung, kidney, liver, muscle, intestine D+1, D+2, D+3

–

–

 Patil, 2018

1

PD-L1

ID P. aer

Lung, blood D+2

–

–

Kidney, liver D+2

–

–

2

PD-L1

IV S. aur

–

–

Lung, spleen D+3

Kidney, liver D+3

–

–

Models including antibacterial agents

 Inoue, 2011 **

1

CTLA-4

CLP

NR

NR

NR

NR

NR

NR

2

CTLA-4

CLP

NR

NR

NR

NR

NR

NR

3

CTLA-4

CLP

NR

NR

NR

NR

NR

NR

4

CTLA-4

CLP + IV C.a.

NR

NR

NR

NR

NR

NR

 Chang, 2013

1

PD-1

CLP + IV C.a.

NR

NR

NR

NR

NR

NR

2

PD-L1

CLP + IV C.a.

NR

NR

NR

NR

NR

NR

3

CTLA-4

CLP + IV C.a.

NR

NR

NR

NR

NR

NR

 Shindo, 2015

1

PD-1

CLP + IV C.a.

NR

NR

NR

NR

NR

NR

 Shindo, 2017

1

PD-L1

CLP + IV C.a.

NR

NR

NR

NR

NR

NR

  1. Exp ID number assigned the experiment(s) providing survival data in each study, C.a. Candida albicans, L. mono Listeria monocytogenes, S. aur Staphylococcus aureus, P. aer Pseudomonas aeruginosa, PD-L1 programmed death ligand-1, PD-1 programmed cell death-1, CTLA-4 cytotoxic T lymphocyte-associated protein-4, BTLA B and T lymphocyte attenuator, CLP cecal ligation and puncture, D day, ID intradermal, IV intravenous, IP intraperitoneal, NR not reported, NA not applicable
  2. *Checkpoint inhibitor administered at D−1 in exp 1 and D0 in exp 2
  3. **Exp 1 administered 50 μg and exp 2 administered 200 μg anti-CTLA-4 in CD-1 mice, exp 3 administered 50 μg anti-CTLA-4 in C57BL6 mice
  4. #Exp 1 performed in C57BL6J mice and exp 2 in Bmal1Mye-/- mice
  5. ##IV Candida challenge 4 days following CLP