Macrophages are one of the principal host cell populations in solid tumors. They 
are capable, due to their plasticity, of acquiring phenotypes that either combat 
(M1 type) or promote (M2 type) neoplastic growth. These cells, known as 
tumor-associated macrophages (TAMs), play complex but pivotal roles in the 
outcome of photodynamic therapy (PDT) of malignant lesions. Among the various 
parenchymal and stromal cell populations found in tumors, TAMs have been shown 
to have the greatest capacity for the uptake of systemically administered 
photosensitizers. Both the tumor-localizing property of photosensitizers and 
their tumor-localized fluorescence could be partly attributed to the activity of 
TAMs. Since resident TAMs with accumulated high photosensitizer content will 
sustain high degrees of PDT damage, this population (predominantly M2 in most 
tumors) is selectively destroyed, and during the ensuing inflammatory reaction 
is replaced with newly invading macrophages of M1 phenotype. These macrophages 
are sentinels responding to DAMP signals from PDT-treated tumor cells and in 
turn are mobilized to generate a variety of inflammatory/immune mediators and 
opsonins. They have a critical role in contributing to the therapeutic effect of 
PDT by mediating disposal of killed cancer cells and by processing/presenting 
tumor antigens to T lymphocytes. However, TAMs accumulating in the later 
post-PDT phase can acquire the M2 (healing) phenotype, and could have a role in 
tumor recurrence by releasing factors that promote angiogenesis and the 
survival/proliferation of remaining cancer cells. Various therapeutic strategies 
modulating TAM activity in the PDT response have potential for clinical use for 
improving PDT-mediated tumor control.