Phytochemical Modulation of T-Lymphocyte Responses in Cancer: Mechanisms, Evidence Gaps and Translational Priorities

Abstract

T lymphocytes are central effectors of tumour immunosurveillance and the principal cellular targets of several successful cancer immunotherapies. Their activity in solid tumours is nevertheless constrained by defective priming, exclusion from tumour nests, suppressive myeloid and regulatory T-cell populations, nutrient competition, chronic antigen exposure and progressive dysfunction. Phytochemicals are increasingly proposed as low-cost immunomodulatory adjuncts, yet the literature often conflates direct tumour cytotoxicity with restoration of T-cell immunity and frequently relies on exposure conditions that are difficult to reproduce clinically. This critical narrative review evaluates how chemically defined plant-derived compounds, selected standardised botanical preparations and microbiota-derived phytochemical metabolites influence anti-tumour T-cell responses. Literature published from 1 January 2000 to 25 May 2026 was selected through live searches of accessible scholarly sources, citation chaining and verification of article identity, relevance and Digital Object Identifiers. Evidence was synthesised around T-cell state, tumour-intrinsic immunogenicity, antigen presentation, myeloid suppression, checkpoint regulation, metabolism, memory formation and combination therapy. Curcuminoids, berberine, sulforaphane, flavonoids, ginsenosides, platycodins, shikonin, tetrandrine, caffeine and urolithin A provide mechanistically diverse preclinical signals. The strongest studies use immunocompetent models, immune-cell depletion or pathway perturbation to show T-cell dependence; weaker studies infer immune enhancement from infiltration, checkpoint expression or tumour shrinkage alone. Bidirectional effects are common: curcumin, resveratrol and shikonin can enhance selected anti-tumour pathways while suppressing T-cell activation under other conditions. Human evidence remains sparse. A phase I sulforaphane study reported peripheral myeloid and CD8 T-cell biomarker changes, but no phytochemical has yet shown replicated clinical improvement in T-cell-mediated tumour control or immunotherapy efficacy. Translation therefore requires exposure-matched mechanistic studies, standardised products, lineage-resolved immune endpoints, rational scheduling and biomarker-rich early trials. Phytochemicals should presently be regarded as experimental immunomodulators rather than established cancer immunotherapy adjuncts.