Tertiary lymphoid structures (tertiary lymphoid structures) are organized ectopic immune aggregates that form within or around tumors and function as local sites of B-cell–rich adaptive immunity. They are increasingly used as biomarkers of antitumor immune activity because their presence and characteristics can predict response to immune checkpoint inhibitors, and they have been characterized in relation to complete pathologic response (CPR). Recent studies also show that TLS can be assessed noninvasively by CT imaging in gastric cancer, highlighting a potential imaging-based diagnostic approach. Across tumor types, they are linked to improved prognosis and enhanced immunotherapy response, including in breast cancer and non-small cell lung cancer. Emerging literature also connects TLS biology to spatial proteomics and B-cell signatures, reinforcing their role in the tumor microenvironment as predictors of treatment benefit. Their relevance has been noted in Merkel cell carcinoma, although the TLS–checkpoint inhibitor relationship there remains under evaluation.
Immunotherapy response
- TLS are emerging as important predictors of response to immune checkpoint inhibitors, with presence and characteristics used to stratify likely responders. (PMID:41466351)
- In melanoma, B-cell and humoral immune features within TLS-like structures were linked to regulatory and autoimmune-like features with implications for immunotherapy. (PMID:41792971)
- Spatial proteomics of TLS in Merkel cell carcinoma showed correlation with immunotherapy response. (PMID:41466351)
- TLS were characterized to dissect the immune landscape associated with complete pathologic response in non-small cell lung cancer. (PMID:41805895)
Gastric cancer and imaging
- A multicenter study demonstrated noninvasive CT imaging assessment of TLS in gastric cancer. (PMID:41642706)
- CT-based evaluation was used to assess TLS features associated with immunotherapy response. (PMID:41642706)
- TLS in gastric cancer were associated with improved survival and enhanced response to anticancer immunotherapy. (PMID:41642706)
Breast cancer
- TLS were associated with improved prognosis and immunotherapy response in breast cancer. (PMID:42028730)
- Organized immune aggregates in the tumor microenvironment were linked to better outcomes in breast cancer. (PMID:42028730)
- Review literature highlights therapeutic potential of TLS in breast cancer. (PMID:42028730)
Lung cancer and complete pathologic response
- Structured immune aggregates analyzed alongside B cells were associated with complete pathologic response after perioperative chemoimmunotherapy in non-small cell lung cancer. (PMID:41805895)
- B-cell signatures were decoded to understand CPR-associated immune landscapes in non-small cell lung cancer. (PMID:41805895)
- TLS were evaluated as part of the immune contexture linked to pathologic response. (PMID:41805895)
Merkel cell carcinoma
- Ectopic lymphoid formations within or around tumors were evaluated for correlation with immunotherapy response in Merkel cell carcinoma. (PMID:41466351)
- Spatial proteomics provided mechanistic insight into TLS composition and response association. (PMID:41466351)
- The TLS–checkpoint inhibitor relationship in Merkel cell carcinoma has not yet been fully evaluated. (PMID:41466351)