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Immune cells that have got inside the tumour. More of them means better outcomes in triple-negative breast cancer.
Tumour-infiltrating lymphocytes (TILs) are immune cells that have got inside the tumour, and in Triple-negative breast cancer (TNBC) more of them means better outcomes. Stromal TILs are scored on ordinary H&E slides by the International TILs Working Group method, and their strong prognostic signal in stage I disease has driven de-escalation trials, captured in the idea on TIL-based omission of chemotherapy in stage I TNBC. TILs are also the raw material for TIL therapy, so the term links to that technology and to Digital pathology & AI. It is referenced by Histopathology & immunohistochemistry, Spatial-omics-guided treatment selection, the TNBC roadmap, Carsten Denkert and Sherene Loi, and by the bottlenecks on cold tumours and on predicting immunotherapy response.
Showing the technology this term belongs to: TIL therapy.
The glossary entry explains the word; the readout page carries the scoring rule, the thresholds approvals use, the companion diagnostics and the tests.
The evidence behind the stage I de-escalation statement on the triple-negative page: an ordinary haematoxylin and eosin slide identifies a fifth of patients whose outcome without chemotherapy matches treated cohorts. A prospective trial of chemotherapy omission is the missing step.
This is the population-based prevalence for the two label thresholds in early TNBC, and it shows the KEYNOTE-355 CPS 10 gate would admit only about a quarter of unselected patients.
This trial supplied the randomised proof that was missing for TIL therapy and showed academic centres can run cell-therapy phase 3 trials without industry. It supports TIL as a standard option after checkpoint inhibitor failure in melanoma and underpinned reimbursement in the Netherlands. The comparator, ipilimumab, is itself only modestly effective in this setting, and overall survival did not differ significantly.
Lifileucel proved that Steven Rosenberg's decades-old TIL concept could be industrialised into a licensed product and gave patients with checkpoint-refractory melanoma, who otherwise have few options, a chance of durable remission. It is the first cell therapy approved for any solid tumour. The treatment requires surgery to harvest tumour, hospitalisation for lymphodepletion and IL-2, and specialised centres, so its reach is limited.
The 98% figure shows how much antibody and scoring choices matter: it sits against 14.7% and 23% in the two large series. The tumour-size-dependent effect of T-cell density is a hypothesis about immune exhaustion in bulkier tumours.
The exome-level TMB here (0.82 per megabase) is an order of magnitude below panel estimates, a warning against comparing TMB across assays; and the survival signal sits in the microenvironment, which is where immunotherapy biomarkers for this disease may have to be found.
The Western counterpart to the Indian series, with lower rates and a prognostic signal in the opposite direction from what immunotherapy enthusiasts might hope. The TIGIT and CD155 finding names a second checkpoint for future trials.
TIMER2.0 is one of the most used tools in cancer immunogenomics and its multi-algorithm design is a reminder that computational immune cell estimates are model-dependent and should be cross-checked.
Shares Map which tumour clones sit next to which immune cells before choosing therapy, Standards for spatial and multiplex tissue biomarkers before they reach the clinic, Binnewies 2018: understanding the tumour immune microenvironment for effective therapy, Grow tumour organoids together with the patient's own immune cells.
Shares Li 2020: TIMER2.0 for analysis of tumour-infiltrating immune cells, Li 2017: TIMER, a web server for estimating immune cells in tumour genomic data, Thorsson 2018: the immune landscape of cancer across 10,000 tumours, Binnewies 2018: understanding the tumour immune microenvironment for effective therapy.
Shares A-BRAVE, Sherene Loi, Carcinoma with medullary pattern (medullary breast cancer), PD-L1 combined positive score 10 in triple-negative breast cancer.
Shares Map which tumour clones sit next to which immune cells before choosing therapy, Standards for spatial and multiplex tissue biomarkers before they reach the clinic, Spatial-omics-guided treatment selection, Turn the map of immune cells inside a tumour into a standardised test.
Shares Clinical relevance of PD-L1 expression in gallbladder cancer: a potential target for therapy, Immune microenvironment in gallbladder adenocarcinomas, Programmed death ligand-1 (PD-L1) is an independent negative prognosticator in Western-world gallbladder cancer, Unraveling triple-negative breast cancer tumor microenvironment heterogeneity: towards an optimized treatment approach.
Shares Clinical relevance of PD-L1 expression in gallbladder cancer: a potential target for therapy, Immune microenvironment in gallbladder adenocarcinomas, Programmed death ligand-1 (PD-L1) is an independent negative prognosticator in Western-world gallbladder cancer, PD-L1 IC score (immune-cell score, SP142).
Shares Immunomodulatory triple-negative breast cancer (IM), Comparison of SP142 and 22C3 PD-L1 assays in a population-based cohort of triple-negative breast cancer patients in the context of their clinically established scoring algorithms, PD-L1 combined positive score 10 in triple-negative breast cancer, TNBC roadmap: from 'nothing to target' to ADC + immunotherapy first line.
Shares Immunomodulatory triple-negative breast cancer (IM), Comparison of SP142 and 22C3 PD-L1 assays in a population-based cohort of triple-negative breast cancer patients in the context of their clinically established scoring algorithms, PD-L1 combined positive score 10 in triple-negative breast cancer, Turn the map of immune cells inside a tumour into a standardised test.