Table 4 In vivo experiments related to CD8⁺ T cells

Glioblastoma

Neoantigen vaccine

Designed a neoantigen-personalized tumor vaccine for glioblastoma patients, which successfully promoted the anti-tumor response of CD8⁺ T cells

Limited for patients who did not receive dexamethasone during vaccine priming;

post vaccination, T cells expressed multiple co-inhibitory receptors

[188]

NSCLC

Neoadjuvant therapy

lymph node metastases, cancer microvessels and cancer‐associated fibroblasts promote CD8⁺ T cell exclusion and dysfunction

Limited cohort; uncertain whether the setting of a positive threshold during the image analysis; lack of functional tests on T cells and other immune cells

[189]

NSCLC

Anti PD-1 treatment

CD103⁺CD8⁺ infiltrating lymphocytes could serve as a predictive biomarker for PD-1 based immunotherapy

Uncertain CD103⁺CD8⁺ TILs are enriched for tumor antigen specific CTL

[190]

NSCLC

ICB

find a relationship between self-renewing CD8⁺ T cells and response of cancer patients to PD-1 blockade

Cannot exclude the intrinsic difference in patients

[191]

NSCLC

Bevacizumab combined with anti PD-1 treatment

improved abnormal tumor vessels and enhanced T lymphocytes cytotoxic and prolong patient’s survival time function of CD8⁺ T cells in lung cancer

Unknown how to integrate VEGF/VEGFR inhibitors combine with ICIs and the mechanisms needed to elucidate

[192]

NSCLC

4-1BB agonism combining with anti PD-L1

anti PD-L1 combine with 4-1BB induced further tumor regression and enhanced survival in tumor-bearing mice

Need make deeper characterizations of the CD103^+/− CD8⁺ T cells beyond immune molecules

[193]

NSCLC

ICB

CD28 is advocated as a key determinant in CD8 T cells and provides feasible biomarkers of ICB response

CD137 and ICOS failed to provide functional advantage to CD28⁻ T cells in the tumor site;

cannot rule out that a fraction of intra-tumor PD1⁺CD28⁻ T cells

[194]

NSCLC

anti PD-L1 treatment

identified a heterogeneous population of neoantigen-specific CD8⁺ T cells with a late effector-like phenotype

limited pre- and post-treatment patient samples

[195]

ESCC

NICB

CD8⁺ Tex-SPRY1 cells predict response, interactions with macrophages and B cells, enhance ICB response and improved survival for ICB therapy

Unclear whether the regulation of progenitor cell like CD8⁺ Tex cells interacting with other immune cells contributes to the immunotherapy response

[196]

Cervical cancer

HPV E6/E7-targeted therapeutic vaccination

combined with radiotherapy

CD103 is a biomarker for tumor-reactive T cell infiltration of cervical cancers and E6/E7-targeted immunotherapy

Unknown the precise differentiation status of CD8 coexpression in cervical cancer

[197]

Melanoma

pembrolizumab

Tumor-resident CD8⁺ T-cell numbers are more prognostic than total CD8⁺ T cells

Absence of information on subsets that can not determine whether the protective response was associated with any particular subset

[198]

Melanoma

BzATP

P2RX7 stimulation is a novel therapeutic treatment to enhance tumor immunotherapy

unclear what role P2RX7 would play in adoptive immunotherapy by CD8⁺ T cells; need for careful evaluation of how tumor-specific T cells are activated in order to address whether P2RX7 plays a beneficial role

[199

BC

ICB

CD8⁺ T_RM cells contribute to BC immuno- surveillance and are the key targets of modulation by immune checkpoint inhibition

Unclear the direct or indirect mechanisms in vivo

[200]

Melanoma

Activin-A

activin-A offer new therapeutic opportunities to overcome CD8⁺ T cell exclusion and immunotherapy resistance

Limited bioavailability in Tregs or CD4⁺ T cell; unclear the potential roles of DCs and of monocyte recruitment by CCR4 ligands

[201]

CRC

radical-intent resection of the primary tumor

CD8⁺ MeTIL markers could measure CD8⁺ TILs distributions

Low proportion of stage IV disease in this cohorts, and more metastatic tumors are needed

[202]

BC

radical cystectomy and adjuvant chemotherapy

TIGIT⁺ CD8⁺ T-cells were associated with suppressive immune contexture and it can regard as a biomarker for treatment

Unknown the mechanism of TIGIT shaping the dysfunction state of CD8⁺ T cells and the synergistic effect of double immune checkpoint blockade in BC were worthy of further study

[203]

HCC

δ-Catenin peptide vaccines

active CTLs, enhance the infiltration of CD8⁺ T cells into tumors and enhance the secretion of IFN-γ

Didn’t check the therapy effects ofδ-Catenin peptide vaccines combined with anti-CTLA-4 or anti-PD-1 mAbs

[204]