Table 3 Representative studies revealing ITH of tumor-infiltrating lymphocytes

NSCLC

[66]

Spatial heterogeneity

Tumor-infiltrating T cells

Ubiquitous and multi-regional tumors

Numbers of expanded ubiquitous or regional intratumoral TCRs are not associated with outcome

LC

[41]

Spatial heterogeneity

CD8 + T cell infiltration

Multi-regional tumors

High clonal neoantigen load and low immune evasion capacity are associated with improved disease-free survival times

Localized LUAD

[72]

Spatial heterogeneity

CD4 + and CD8 + T cells

Centers and margins of tumors

Amount and TCR repertoire ITH of CD4 + and CD8 + TILs in tumor centers and margins are associated with prognosis

Localized LUAD

[65]

Spatial heterogeneity

T cell density and clonality

Multi-regional tumors

ITH in the T cell repertoire is associated with a risk of relapse

Early LUAD

[265]

Spatial heterogeneity

Immune cell atlas

Tumor, adjacent tissue and blood

N/A

ESCC

[266]

Spatial heterogeneity

TCR landscape and PD-L1 expression

Multi-regional tumors, normal tissues and blood samples

High proportion of branch neoantigens is associated with short overall survival

ESCC

[119]

Spatial heterogeneity

T cell clonality

Multi-regional tumors, matched adjacent normal tissue and peripheral blood

N/A

CRC

[267]

Spatial heterogeneity

T cell clones and counts

Tumor and adjacent tissue

N/A

GBM

[84]

Spatial heterogeneity

TIL diversity

Multi-regional tumors

Overall level of the immune response is connected with prognosis

OC

[268]

Spatial heterogeneity

T cell clonality

Multi-regional tumors

Combination of mutational processes and immune properties is associated with prognosis

NPC

[168]

Spatial heterogeneity

T cell clonality

Matched tumor, adjacent normal tissue and peripheral blood

A lower diversity of TCR repertoire in tumors than paired tissues or a low similarity between the paired tissues is associated with a poor prognosis

MEL and CRC

[269]

Spatial heterogeneity

T cell clonality

Multi-regional tumors

N/A

MEL

[166]

Spatial heterogeneity

T cell clonality

Metastases

Homogeneous lesions are associated with response to therapy;

MEL

[270]

Spatial heterogeneity

Single-cell analyses of T cells

Metastases

N/A

HCC

[53]

Spatial heterogeneity

CD8 + T cells infiltration and immune markers

Multifocal tumors

N/A

PC

[105]

Spatial heterogeneity

T cell clonality

Multi-regional tumors and peripheral blood

N/A

RCC

[271]

Spatial heterogeneity

The clonal composition of T cell populations

Multi-regional tumors

N/A

OC

[272]

Spatial heterogeneity

T cell oligoclonal expansion

Metastases

N/A

OC

[273]

Spatial heterogeneity

T cell clonality

Tumor and peripheral blood

N/A

BC

[274]

Spatial heterogeneity

T cell clonality

Tumors and lymph nodes

N/A

NSCLC

[127]

Heterogeneity among different levels of PD-1 expression

Transcriptional and metabolic profile of T cells

Different subsets of CD8 + TILs

Presence of PD-1 T cells is associated with both response and survival in patients treated with PD-1 blockade

Metastatic MEL

[275]

Heterogeneity among different levels of PD-1 expression

T cell clonality

Metastases

N/A

Metastatic MEL

[126]

Heterogeneity among different levels of PD-1 expression

Phenotypic traits of CD8⁺ TILs and TCR clonotype

Metastases

N/A

CC

[125]

Temporal heterogeneity

Circulating TCR repertoire

Peripheral blood samples throughout carcinogenesis

Less clonotypes in TCR repertoire of sentinel lymphatic node is associated with poor prognosis

GC

[67]

Temporal heterogeneity

TCR repertoire

Tissue samples at different pathological stages

An 11-gene module related to TCR repertoire is correlated with the overall survival of GC patients

LC

[73]

Temporal heterogeneity

Circulating TCR repertoire

Pre- and post-treatment peripheral blood samples

Increased diversity and high overlap rate between the pre- and post-treatment TCR repertoires indicated clinical benefit

NPC

[74]

Temporal heterogeneity

Circulating TCR repertoire

pairwise pre-treatment and post-treatment peripheral blood samples

Ascending TCR diversity and higher similarity between pre- and post-treatment samples showed better distant metastasis-free survival

RCC

[75]

Temporal heterogeneity

Circulating TCR repertoire

peripheral leukocyte samples before and after surgery

Higher baseline TCRB diversity is associated with better prognosis of in stage IV patients

NSCLC

[276]

Temporal heterogeneity

Circulating TCR repertoire

blood samples before and 6 weeks after immunotherapy, and disease progression

the diversity of TCR repertoire and singletons in the TCRβ pool increased after immunotherapy

LUAD

[277]

Temporal heterogeneity

Circulating TCR repertoire

Peripheral blood samples

Higher baseline circulating TCRB diversity was associated with better prognosis

The chemotherapeutic agents for advanced lung cancer do not affect adaptive immune function over the first few treatment cycles

MEL in mouse model

[278]

Temporal heterogeneity

TCR repertoire

tumor, draining lymph node (dLN) and peripheral blood samples

N/A

CRC

[279]

Spatial heterogeneity and temporal heterogeneity

Immunoscore (derived from the CD3 + /CD8 + T cell densities)

Spatiotemporally distinct sites of metastases

High immunoscore is associated with the lowest recurrence risk