Table 2 Immunotherapy of lung cancer with MPE

Target T cells

Minimally invasive technologies

Specific T cells

Screen patients who are susceptible to T cell-targeted therapies

[35]

Intrapleural administration of IL-2

CD8⁺T cells,

CD3⁺T cells

Prolong patients survival, alleviate pleurisy

[129, 130, 132]

Adoptive cell therapy

CAR-T

CEA

Phase I clinical trial: evaluate the efficacy and safety of CAR-T therapy

NCT02349724

NCT04348643

GPC3

Eliminate GPC-expressing LSCC cells and produce cytokines(IL-2,IL-10,IFN-γ,TNF-α)

[148]

HER2

Afatinib is a treatment option for HER2 mutation-positive NSCLC

[151]

/

Exhibit acceptable toxicity in phase I/II studies

NCT01935843

MSLN

Inject CAR-T cells is better than systemic infusion of T cells

NCT01583686

NCT02414269

PD-L1

Killing effect enhanced and proliferation rate of tumor cells was low

[156]

ROR1

Microphysiological 3D models exhibited anti-tumor activity

[160]

EGFR

Phase I trial: EGFR-CAR-T cells infusion was tested in NSCLC patients

NCT01869166

166

/

Evaluate CXCR-5-modified anti-EGFR-CAR T cells immunotherapy

NCT04153799

MUC1

Anti-MUC1-CAR T cells is used in an open Phase I/II clinical trial

NCT02587689

/

Phase I/II trial: evaluate anti-MUC1 CAR-T cells with PD-1 gene knockout

NCT03525782

/

MUC1-CAR T cells treatment in phase I/II study

NCT02587689

/

MUC1-CAR-pNK cells study: implant CAR structure into NK cells

NCT02839954

/

CAR-T cells target TnMUC1 in a phase I trail

NCT04025216

FAP

Phase I clinical trial: anti-FAP-Δ-CD28/CD3ζ CAR-T cells with PD-1 inhibition improved survival

NCT01722149

[169]

ICB

CTLA-4

Ipilimumab

Added carboplatin and paclitaxel didn’t prolong NSCLC PFS or OS

[174, 175]

PD-1/PD-L1

Pembrolizumab

Improve OS (12.7 vs 8.5 months)

[186]

/

Improves PFS, OS and efficacy rates

[187]

Nivolumab

Improved efficacy rates (20% vs 9%), PFS (3.5 vs 2.8 months) and 5-year OS (13% vs 3%)

[188, 189]

Atezolizumab

Median OS prolong 7.1 months and incidence of garde 3/4 adverse events was low

[190]

Durvalumab

Phase III Pacific trial: the median PFS(16.8 vs 5.6 months) was improved

[191]

/

4-year median OS (47.5 vs 29.1 months), 4-year OS rate(49.6% vs 36.3%) and 4-year PFS rate (35.3% vs 19.5%) improved

[192]

Nivolumab + Ipilimumab

Efficacy rates, median survival (17.1 vs 13.9 months), 2-year OS rate (40% vs 32.8%) improved and incidence of adverse reactions (32.8% vs 36%) decreased

[195]

Tregs

CCR4 antagonist

Tregs

CCR4 and CTLA-4 inhibitors increase efficacy greatly

[201]

IL-1 blockers

CCL22

Inhibit tumor-induced immunosuppression by attracting CCL22

[202]

Target TNFR2

Tregs

Antitumor activity of CD8⁺T cells was enhanced remarkablely

[70]

TAMs

PA-MSHA

NKs

Pleural effusion gradually reduced in 12 h

[206, 207]

mAb, vaccines, antisense oligonucleotides, small molecule inhibitors

TGF-β

Reverse immune suppression using antisense gene

[208]

Fucoidan

NK-κB

Inhibit tumor cells migration, CCL22 generation and CD4⁺T cells recruitment

[211]

DCs

DCs are reinfused to thoracic cavity

CD34⁺stem-cells

The overall response rate was 54%, the median duration of response was 20 weeks

[212]

DC-CIK

DCs

The overall response rate was 38% and the disease control rate was 70.3%

[215]

DC vaccine therapy combined with ICB

CD8 + T cells

Show anti-tumor effect

[216]

MDSCs

Peptide-Fc fusion protein

S100A protein family

Eliminate MDSCs

[218]

CSF-1R

TAMs, PMN-MDSCs

Boost anti-PD-1 immunotherapy efficacy

[225]

PDE-5 inhibitors

MDSCs

Reinvigorate anti-tumor immune responses and prolong survival in vivo

[227, 228]

Paclitaxel

MDSCs

Promote MDSCs differentiation into DCs in MPE

[229]

NKs

Intrapleural administration of IL-2

NKs

MPE disappeared and didn’t recurrent more than 2 years

[234,235,236,237]

IL-15

NKs

Antagonize the inhibitory effects of TME and not cause corresponding toxicity

[107]